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What is (are) L1 syndrome ? | L1 syndrome is an inherited disorder that primarily affects the nervous system. L1 syndrome involves a variety of features that were once thought to be distinct disorders, but are now considered to be part of the same syndrome. The most common characteristics of L1 syndrome are muscle stiffness (spasticity) of the lower limbs, intellectual disability, increased fluid in the center of the brain (hydrocephalus), and thumbs bent toward the palm (adducted thumbs). People with L1 syndrome can also have difficulty speaking (aphasia), seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum). The symptoms of L1 syndrome vary widely among affected individuals, even among members of the same family. Because this disorder involves spasticity of the lower limbs, L1 syndrome is sometimes referred to as spastic paraplegia type 1 (SPG1). | L1 syndrome |
How many people are affected by L1 syndrome ? | L1 syndrome is estimated to occur in 1 in 25,000 to 60,000 males. Females are rarely affected by this condition. | L1 syndrome |
What are the genetic changes related to L1 syndrome ? | L1 syndrome is caused by mutations in the L1CAM gene. The L1CAM gene provides instructions for producing the L1 protein, which is found throughout the nervous system on the surface of nerve cells (neurons). The L1 protein plays a role in the development and organization of neurons, the formation of the protective sheath (myelin) that surrounds certain neurons, and the formation of junctions between nerve cells (synapses), where cell-to-cell communication occurs. Mutations in the L1 protein can interfere with these developmental processes. Research suggests that a disruption in the development and function of neurons causes the signs and symptoms of L1 syndrome. | L1 syndrome |
Is L1 syndrome inherited ? | This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. | L1 syndrome |
What are the treatments for L1 syndrome ? | These resources address the diagnosis or management of L1 syndrome: - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview - Gene Review: Gene Review: L1 Syndrome - Genetic Testing Registry: Corpus callosum, partial agenesis of, X-linked - Genetic Testing Registry: L1 Syndrome - Genetic Testing Registry: Spastic paraplegia 1 - Genetic Testing Registry: X-linked hydrocephalus syndrome These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | L1 syndrome |
What is (are) acute promyelocytic leukemia ? | Acute promyelocytic leukemia is a form of acute myeloid leukemia, a cancer of the blood-forming tissue (bone marrow). In normal bone marrow, hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In acute promyelocytic leukemia, immature white blood cells called promyelocytes accumulate in the bone marrow. The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition. People with acute promyelocytic leukemia are especially susceptible to developing bruises, small red dots under the skin (petechiae), nosebleeds, bleeding from the gums, blood in the urine (hematuria), or excessive menstrual bleeding. The abnormal bleeding and bruising occur in part because of the low number of platelets in the blood (thrombocytopenia) and also because the cancerous cells release substances that cause excessive bleeding. The low number of red blood cells (anemia) can cause people with acute promyelocytic leukemia to have pale skin (pallor) or excessive tiredness (fatigue). In addition, affected individuals may heal slowly from injuries or have frequent infections due to the loss of normal white blood cells that fight infection. Furthermore, the leukemic cells can spread to the bones and joints, which may cause pain in those areas. Other general signs and symptoms may occur as well, such as fever, loss of appetite, and weight loss. Acute promyelocytic leukemia is most often diagnosed around age 40, although it can be diagnosed at any age. | acute promyelocytic leukemia |
How many people are affected by acute promyelocytic leukemia ? | Acute promyelocytic leukemia accounts for about 10 percent of acute myeloid leukemia cases. Acute promyelocytic leukemia occurs in approximately 1 in 250,000 people in the United States. | acute promyelocytic leukemia |
What are the genetic changes related to acute promyelocytic leukemia ? | The mutation that causes acute promyelocytic leukemia involves two genes, the PML gene on chromosome 15 and the RARA gene on chromosome 17. A rearrangement of genetic material (translocation) between chromosomes 15 and 17, written as t(15;17), fuses part of the PML gene with part of the RARA gene. The protein produced from this fused gene is known as PML-RAR. This mutation is acquired during a person's lifetime and is present only in certain cells. This type of genetic change, called a somatic mutation, is not inherited. The PML-RAR protein functions differently than the protein products of the normal PML and RARA genes. The protein produced from the RARA gene, RAR, is involved in the regulation of gene transcription, which is the first step in protein production. Specifically, this protein helps control the transcription of certain genes important in the maturation (differentiation) of white blood cells beyond the promyelocyte stage. The protein produced from the PML gene acts as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. The PML-RAR protein interferes with the normal function of both the PML and the RAR proteins. As a result, blood cells are stuck at the promyelocyte stage, and they proliferate abnormally. Excess promyelocytes accumulate in the bone marrow and normal white blood cells cannot form, leading to acute promyelocytic leukemia. The PML-RARA gene fusion accounts for up to 98 percent of cases of acute promyelocytic leukemia. Translocations involving the RARA gene and other genes have been identified in a few cases of acute promyelocytic leukemia. | acute promyelocytic leukemia |
Is acute promyelocytic leukemia inherited ? | Acute promyelocytic leukemia is not inherited but arises from a translocation in the body's cells that occurs after conception. | acute promyelocytic leukemia |
What are the treatments for acute promyelocytic leukemia ? | These resources address the diagnosis or management of acute promyelocytic leukemia: - American Cancer Society: Diagnosis of Acute Myeloid Leukemia - American Cancer Society: Treatment of Acute Promyelocytic (M3) Leukemia - Genetic Testing Registry: Acute promyelocytic leukemia - MedlinePlus Encyclopedia: Acute Myeloid Leukemia - National Cancer Institute: Adult Acute Myeloid Leukemia Treatment - National Cancer Institute: Leukemia - National Heart Lung and Blood Institute: Bone Marrow Tests These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | acute promyelocytic leukemia |
What is (are) renal hypouricemia ? | Renal hypouricemia is a kidney (renal) disorder that results in a reduced amount of uric acid in the blood. Uric acid is a byproduct of certain normal chemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, having too much uric acid in the body is toxic, so excess uric acid is removed from the body in urine. People with renal hypouricemia have little to no uric acid in their blood; they release an excessive amount of it in the urine. In many affected individuals, renal hypouricemia causes no signs or symptoms. However, some people with this condition develop kidney problems. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in their sides and lower back as well as nausea and vomiting that can last several hours. Because an excessive amount of uric acid passes through the kidneys to be excreted in urine in people with renal hypouricemia, they have an increased risk of developing kidney stones (nephrolithiasis) formed from uric acid crystals. These uric acid stones can damage the kidneys and lead to episodes of blood in the urine (hematuria). Rarely, people with renal hypouricemia develop life-threatening kidney failure. | renal hypouricemia |
How many people are affected by renal hypouricemia ? | The prevalence of renal hypouricemia is unknown; at least 150 affected individuals have been described in the scientific literature. This condition is thought to be most prevalent in Asian countries such as Japan and South Korea, although affected individuals have been found in Europe. Renal hypouricemia is likely underdiagnosed because it does not cause any symptoms in many affected individuals. | renal hypouricemia |
What are the genetic changes related to renal hypouricemia ? | Mutations in the SLC22A12 or SLC2A9 gene cause renal hypouricemia. These genes provide instructions for making proteins called urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), respectively. These proteins are found in the kidneys, specifically in structures called proximal tubules. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete unneeded substances into the urine. Within the proximal tubules, both the URAT1 and GLUT9 proteins reabsorb uric acid into the bloodstream or release it into the urine, depending on the body's needs. Most uric acid that is filtered through the kidneys is reabsorbed into the bloodstream; about 10 percent is released into urine. Mutations that cause renal hypouricemia lead to the production of URAT1 or GLUT9 protein with a reduced ability to reabsorb uric acid into the bloodstream. Instead, large amounts of uric acid are released in the urine. The specific cause of the signs and symptoms of renal hypouricemia is unclear. Researchers suspect that when additional uric acid is produced during exercise and passed through the kidneys, it could lead to tissue damage. Alternatively, without the antioxidant properties of uric acid, free radicals could cause tissue damage in the kidneys. Another possibility is that other substances are prevented from being reabsorbed along with uric acid; accumulation of these substances in the kidneys could cause tissue damage. It is likely that individuals with renal hypouricemia who have mild or no symptoms have enough protein function to reabsorb a sufficient amount of uric acid into the bloodstream to prevent severe kidney problems. | renal hypouricemia |
Is renal hypouricemia inherited ? | This condition is typically inherited in an autosomal recessive pattern, which means both copies of the SLC22A12 or SLC2A9 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition. Sometimes, individuals with one SLC2A9 gene mutation in each cell have reduced levels of uric acid. The levels usually are not as low as they are in people who have mutations in both copies of the gene, and they often do not cause any signs or symptoms. Rarely, people who carry one copy of the mutated gene will develop uric acid kidney stones. | renal hypouricemia |
What are the treatments for renal hypouricemia ? | These resources address the diagnosis or management of renal hypouricemia: - Genetic Testing Registry: Familial renal hypouricemia - Genetic Testing Registry: Renal hypouricemia 2 - KidsHealth from Nemours: Blood Test: Uric Acid - MedlinePlus Encyclopedia: Uric Acid--Blood These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | renal hypouricemia |
What is (are) GM1 gangliosidosis ? | GM1 gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Some researchers classify this condition into three major types based on the age at which signs and symptoms first appear. Although the three types differ in severity, their features can overlap significantly. Because of this overlap, other researchers believe that GM1 gangliosidosis represents a continuous disease spectrum instead of three distinct types. The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually become apparent by the age of 6 months. Infants with this form of the disorder typically appear normal until their development slows and muscles used for movement weaken. Affected infants eventually lose the skills they had previously acquired (developmentally regress) and may develop an exaggerated startle reaction to loud noises. As the disease progresses, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, seizures, profound intellectual disability, and clouding of the clear outer covering of the eye (the cornea). Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. In some cases, affected individuals have distinctive facial features that are described as "coarse," enlarged gums (gingival hypertrophy), and an enlarged and weakened heart muscle (cardiomyopathy). Individuals with GM1 gangliosidosis type I usually do not survive past early childhood. Type II GM1 gangliosidosis consists of intermediate forms of the condition, also known as the late infantile and juvenile forms. Children with GM1 gangliosidosis type II have normal early development, but they begin to develop signs and symptoms of the condition around the age of 18 months (late infantile form) or 5 years (juvenile form). Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, distinctive facial features, or enlarged organs. Type II usually progresses more slowly than type I, but still causes a shortened life expectancy. People with the late infantile form typically survive into mid-childhood, while those with the juvenile form may live into early adulthood. The third type of GM1 gangliosidosis is known as the adult or chronic form, and it represents the mildest end of the disease spectrum. The age at which symptoms first appear varies in GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. The characteristic features of this type include involuntary tensing of various muscles (dystonia) and abnormalities of the spinal bones (vertebrae). Life expectancy varies among people with GM1 gangliosidosis type III. | GM1 gangliosidosis |
How many people are affected by GM1 gangliosidosis ? | GM1 gangliosidosis is estimated to occur in 1 in 100,000 to 200,000 newborns. Type I is reported more frequently than the other forms of this condition. Most individuals with type III are of Japanese descent. | GM1 gangliosidosis |
What are the genetic changes related to GM1 gangliosidosis ? | Mutations in the GLB1 gene cause GM1 gangliosidosis. The GLB1 gene provides instructions for making an enzyme called beta-galactosidase (-galactosidase), which plays a critical role in the brain. This enzyme is located in lysosomes, which are compartments within cells that break down and recycle different types of molecules. Within lysosomes, -galactosidase helps break down several molecules, including a substance called GM1 ganglioside. GM1 ganglioside is important for normal functioning of nerve cells in the brain. Mutations in the GLB1 gene reduce or eliminate the activity of -galactosidase. Without enough functional -galactosidase, GM1 ganglioside cannot be broken down when it is no longer needed. As a result, this substance accumulates to toxic levels in many tissues and organs, particularly in the brain. Progressive damage caused by the buildup of GM1 ganglioside leads to the destruction of nerve cells in the brain, causing many of the signs and symptoms of GM1 gangliosidosis. In general, the severity of GM1 gangliosidosis is related to the level of -galactosidase activity. Individuals with higher enzyme activity levels usually have milder signs and symptoms than those with lower activity levels because they have less accumulation of GM1 ganglioside within the body. Conditions such as GM1 gangliosidosis that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. | GM1 gangliosidosis |
Is GM1 gangliosidosis inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | GM1 gangliosidosis |
What are the treatments for GM1 gangliosidosis ? | These resources address the diagnosis or management of GM1 gangliosidosis: - Genetic Testing Registry: Gangliosidosis GM1 type 3 - Genetic Testing Registry: Gangliosidosis generalized GM1 type 1 - Genetic Testing Registry: Infantile GM1 gangliosidosis - Genetic Testing Registry: Juvenile GM>1< gangliosidosis These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | GM1 gangliosidosis |
What is (are) giant axonal neuropathy ? | Giant axonal neuropathy is an inherited condition involving dysfunction of a specific type of protein in nerve cells (neurons). The protein is essential for normal nerve function because it forms neurofilaments. Neurofilaments make up a structural framework that helps to define the shape and size of the neurons. This condition is characterized by abnormally large and dysfunctional axons, which are the specialized extensions of nerve cells that are required for the transmission of nerve impulses. Giant axonal neuropathy generally appears in infancy or early childhood. It progresses slowly as neuronal injury becomes more severe. Signs of giant axonal neuropathy usually begin in the peripheral nervous system, which governs movement and sensation in the arms, legs, and other parts of the body. Most individuals with this disorder first have problems with walking. Later they may lose sensation, coordination, strength, and reflexes in their limbs. Hearing and visual problems may also occur. Extremely kinky hair (as compared to others in the family) is characteristic of giant axonal neuropathy, occurring in almost all affected people. As the disorder progresses, the brain and spinal cord (central nervous system) may become involved, causing a gradual decline in mental function, loss of control of body movement, and seizures. | giant axonal neuropathy |
How many people are affected by giant axonal neuropathy ? | Giant axonal neuropathy is a very rare disorder; the incidence is unknown. | giant axonal neuropathy |
What are the genetic changes related to giant axonal neuropathy ? | Giant axonal neuropathy is caused by mutations in the GAN gene, which provides instructions for making a protein called gigaxonin. Some GAN gene mutations change the shape of the protein, affecting how it binds to other proteins to form a functional complex. Other mutations prevent cells from producing any gigaxonin protein. Gigaxonin is involved in a cellular function that destroys and gets rid of excess or damaged proteins using a mechanism called the ubiquitin-proteasome system. Neurons without functional gigaxonin accumulate excess neurofilaments in the axon, causing the axons to become distended. These giant axons do not transmit signals properly and eventually deteriorate, resulting in problems with movement and other nervous system dysfunction. | giant axonal neuropathy |
Is giant axonal neuropathy inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | giant axonal neuropathy |
What are the treatments for giant axonal neuropathy ? | These resources address the diagnosis or management of giant axonal neuropathy: - Gene Review: Gene Review: Giant Axonal Neuropathy - Genetic Testing Registry: Giant axonal neuropathy These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | giant axonal neuropathy |
What is (are) Waldenstrm macroglobulinemia ? | Waldenstrm macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells called lymphoplasmacytic cells in the bone marrow. This condition is classified as a lymphoplasmacytic lymphoma. The abnormal cells have characteristics of both white blood cells (lymphocytes) called B cells and of more mature cells derived from B cells known as plasma cells. These abnormal cells produce excess amounts of IgM, a type of protein known as an immunoglobulin; the overproduction of this large protein is how the condition got its name ("macroglobulinemia"). Waldenstrm macroglobulinemia usually begins in a person's sixties and is a slow-growing (indolent) cancer. Some affected individuals have elevated levels of IgM and lymphoplasmacytic cells but no symptoms of the condition; in these cases, the disease is usually found incidentally by a blood test taken for another reason. These individuals are diagnosed with smoldering (or asymptomatic) Waldenstrm macroglobulinemia. It can be several years before this form of the condition progresses to the symptomatic form. Individuals with symptomatic Waldenstrm macroglobulinemia can experience general symptoms such as fever, night sweats, and weight loss. Several other signs and symptoms of the condition are related to the excess IgM, which can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. Features related to hyperviscosity syndrome include bleeding in the nose or mouth, blurring or loss of vision, headache, dizziness, and difficulty coordinating movements (ataxia). In some affected individuals, the IgM proteins clump together in the hands and feet, where the body temperature is cooler than at the center of the body. These proteins are then referred to as cryoglobulins, and their clumping causes a condition known as cryoglobulinemia. Cryoglobulinemia can lead to pain in the hands and feet or episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperatures. The IgM protein can also build up in organs such as the heart and kidneys, causing a condition called amyloidosis, which can lead to heart and kidney problems. Some people with Waldenstrm macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). Doctors are unsure why this feature occurs, although they speculate that the IgM protein attaches to the protective covering of nerve cells (myelin) and breaks it down. The damaged nerves cannot carry signals normally, leading to neuropathy. Other features of Waldenstrm macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy). In the bone marrow, the lymphoplasmacytic cells interfere with normal blood cell development, causing a shortage of normal blood cells (pancytopenia). Excessive tiredness (fatigue) due to a reduction in red blood cells (anemia) is common in affected individuals. People with Waldenstrm macroglobulinemia have an increased risk of developing other cancers of the blood or other tissues. | Waldenstrm macroglobulinemia |
How many people are affected by Waldenstrm macroglobulinemia ? | Waldenstrm macroglobulinemia affects an estimated 3 per million people each year in the United States. Approximately 1,500 new cases of the condition are diagnosed each year in this country, and whites are more commonly affected than African Americans. For unknown reasons, the condition occurs twice as often in men than women. | Waldenstrm macroglobulinemia |
What are the genetic changes related to Waldenstrm macroglobulinemia ? | Waldenstrm macroglobulinemia is thought to result from a combination of genetic changes. The most common known genetic change associated with this condition is a mutation in the MYD88 gene, which is found in more than 90 percent of affected individuals. Another gene commonly associated with Waldenstrm macroglobulinemia, CXCR4, is mutated in approximately 30 percent of affected individuals (most of whom also have the MYD88 gene mutation). Other genetic changes believed to be involved in Waldenstrm macroglobulinemia have not yet been identified. Studies have found that certain regions of DNA are deleted or added in some people with the condition; however, researchers are unsure which genes in these regions are important for development of the condition. The mutations that cause Waldenstrm macroglobulinemia are acquired during a person's lifetime and are present only in the abnormal blood cells. The proteins produced from the MYD88 and CXCR4 genes are both involved in signaling within cells. The MyD88 protein relays signals that help prevent the self-destruction (apoptosis) of cells, thus aiding in cell survival. The CXCR4 protein stimulates signaling pathways inside the cell that help regulate cell growth and division (proliferation) and cell survival. Mutations in these genes lead to production of proteins that are constantly functioning (overactive). Excessive signaling through these overactive proteins allows survival and proliferation of abnormal cells that should undergo apoptosis, which likely contributes to the accumulation of lymphoplasmacytic cells in Waldenstrm macroglobulinemia. | Waldenstrm macroglobulinemia |
Is Waldenstrm macroglobulinemia inherited ? | Waldenstrm macroglobulinemia is usually not inherited, and most affected people have no history of the disorder in their family. The condition usually arises from mutations that are acquired during a person's lifetime (somatic mutations), which are not inherited. Some families seem to have a predisposition to the condition. Approximately 20 percent of people with Waldenstrm macroglobulinemia have a family member with the condition or another disorder involving abnormal B cells. | Waldenstrm macroglobulinemia |
What are the treatments for Waldenstrm macroglobulinemia ? | These resources address the diagnosis or management of Waldenstrm macroglobulinemia: - American Cancer Society: How is Waldenstrom Macroglobulinemia Diagnosed? - American Cancer Society: How is Waldenstrom Macroglobulinemia Treated? - Genetic Testing Registry: Waldenstrom macroglobulinemia - MD Anderson Cancer Center - MedlinePlus Encyclopedia: Macroglobulinemia of Waldenstrom These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Waldenstrm macroglobulinemia |
What is (are) Birt-Hogg-Dub syndrome ? | Birt-Hogg-Dub syndrome is a rare disorder that affects the skin and lungs and increases the risk of certain types of tumors. Its signs and symptoms vary among affected individuals. Birt-Hogg-Dub syndrome is characterized by multiple noncancerous (benign) skin tumors, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties and become larger and more numerous over time. Affected individuals also have an increased chance of developing cysts in the lungs and an abnormal accumulation of air in the chest cavity (pneumothorax) that may result in the collapse of a lung. Additionally, Birt-Hogg-Dub syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dub syndrome. | Birt-Hogg-Dub syndrome |
How many people are affected by Birt-Hogg-Dub syndrome ? | Birt-Hogg-Dub syndrome is rare; its exact incidence is unknown. This condition has been reported in more than 400 families. | Birt-Hogg-Dub syndrome |
What are the genetic changes related to Birt-Hogg-Dub syndrome ? | Mutations in the FLCN gene cause Birt-Hogg-Dub syndrome. This gene provides instructions for making a protein called folliculin. The normal function of this protein is unknown, but researchers believe that it may act as a tumor suppressor. Tumor suppressors prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to uncontrolled cell growth and the formation of noncancerous and cancerous tumors. Researchers have not determined how FLCN mutations increase the risk of lung problems, such as pneumothorax. | Birt-Hogg-Dub syndrome |
Is Birt-Hogg-Dub syndrome inherited ? | This condition is inherited in an autosomal dominant pattern, which means one copy of the altered FLCN gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Less commonly, the condition results from a new mutation in the gene and occurs in people with no history of the disorder in their family. Having a single mutated copy of the FLCN gene in each cell is enough to cause the skin tumors and lung problems associated with Birt-Hogg-Dub syndrome. However, both copies of the FLCN gene are often mutated in the kidney tumors that occur with this condition. One of the mutations is inherited from a parent, while the other occurs by chance in a kidney cell during a person's lifetime. These genetic changes disable both copies of the FLCN gene, which allows kidney cells to divide uncontrollably and form tumors. | Birt-Hogg-Dub syndrome |
What are the treatments for Birt-Hogg-Dub syndrome ? | These resources address the diagnosis or management of Birt-Hogg-Dub syndrome: - BHD Foundation: Practical Considerations - Gene Review: Gene Review: Birt-Hogg-Dube Syndrome - Genetic Testing Registry: Multiple fibrofolliculomas - MedlinePlus Encyclopedia: Collapsed Lung These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Birt-Hogg-Dub syndrome |
What is (are) pseudocholinesterase deficiency ? | Pseudocholinesterase deficiency is a condition that results in increased sensitivity to certain muscle relaxant drugs used during general anesthesia, called choline esters. These fast-acting drugs, such as succinylcholine and mivacurium, are given to relax the muscles used for movement (skeletal muscles), including the muscles involved in breathing. The drugs are often employed for brief surgical procedures or in emergencies when a breathing tube must be inserted quickly. Normally, these drugs are broken down (metabolized) by the body within a few minutes of being administered, at which time the muscles can move again. However, people with pseudocholinesterase deficiency may not be able to move or breathe on their own for a few hours after the drugs are administered. Affected individuals must be supported with a machine to help them breathe (mechanical ventilation) until the drugs are cleared from the body. People with pseudocholinesterase deficiency may also have increased sensitivity to certain other drugs, including the local anesthetic procaine, and to specific agricultural pesticides. The condition causes no other signs or symptoms and is usually not discovered until an abnormal drug reaction occurs. | pseudocholinesterase deficiency |
How many people are affected by pseudocholinesterase deficiency ? | Pseudocholinesterase deficiency occurs in 1 in 3,200 to 1 in 5,000 people. It is more common in certain populations, such as the Persian Jewish community and Alaska Natives. | pseudocholinesterase deficiency |
What are the genetic changes related to pseudocholinesterase deficiency ? | Pseudocholinesterase deficiency can be caused by mutations in the BCHE gene. This gene provides instructions for making the pseudocholinesterase enzyme, also known as butyrylcholinesterase, which is produced by the liver and circulates in the blood. The pseudocholinesterase enzyme is involved in the breakdown of choline ester drugs. It is likely that the enzyme has other functions in the body, but these functions are not well understood. Studies suggest that the enzyme may be involved in the transmission of nerve signals. Some BCHE gene mutations that cause pseudocholinesterase deficiency result in an abnormal pseudocholinesterase enzyme that does not function properly. Other mutations prevent the production of the pseudocholinesterase enzyme. A lack of functional pseudocholinesterase enzyme impairs the body's ability to break down choline ester drugs efficiently, leading to abnormally prolonged drug effects. Pseudocholinesterase deficiency can also have nongenetic causes. In these cases, the condition is called acquired pseudocholinesterase deficiency; it is not inherited and cannot be passed to the next generation. Activity of the pseudocholinesterase enzyme can be impaired by kidney or liver disease, malnutrition, major burns, cancer, or certain drugs. | pseudocholinesterase deficiency |
Is pseudocholinesterase deficiency inherited ? | When due to genetic causes, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive disorder have one copy of the altered gene in each cell and are called carriers. They can pass on the gene mutation to their children, but they do not usually experience signs and symptoms of the disorder. In some cases, carriers of BCHE gene mutations take longer than usual to clear choline ester drugs from the body, but not as long as those with two copies of the altered gene in each cell. | pseudocholinesterase deficiency |
What are the treatments for pseudocholinesterase deficiency ? | These resources address the diagnosis or management of pseudocholinesterase deficiency: - MedlinePlus Encyclopedia: Cholinesterase (blood test) These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | pseudocholinesterase deficiency |
What is (are) warfarin sensitivity ? | Warfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis). Many people with warfarin sensitivity take longer than normal to break down (metabolize) warfarin, so the medication is in their body longer than usual and they require lower doses. These individuals are classified as "slow metabolizers" of warfarin. Other people with warfarin sensitivity do not need as much drug to prevent clots because their clot forming process is already slower than average and can be inhibited by low warfarin doses. If people with warfarin sensitivity take the average dose (or more) of warfarin, they are at risk of an overdose, which can cause abnormal bleeding in the brain, gastrointestinal tract, or other tissues, and may lead to serious health problems or death. Warfarin sensitivity does not appear to cause any health problems other than those associated with warfarin drug treatment. | warfarin sensitivity |
How many people are affected by warfarin sensitivity ? | The prevalence of warfarin sensitivity is unknown. However, it appears to be more common in people who are older, those with lower body weights, and individuals of Asian ancestry. Of the approximately 2 million people in the U.S. who are prescribed warfarin annually, 35,000 to 45,000 individuals go to hospital emergency rooms with warfarin-related adverse drug events. While it is unclear how many of these events are due to warfarin sensitivity, the most common sign is excessive internal bleeding, which is often seen when individuals with warfarin sensitivity are given too much of the medication. | warfarin sensitivity |
What are the genetic changes related to warfarin sensitivity ? | Many genes are involved in the metabolism of warfarin and in determining the drug's effects in the body. Certain common changes (polymorphisms) in the CYP2C9 and VKORC1 genes account for 30 percent of the variation in warfarin metabolism due to genetic factors. Polymorphisms in other genes, some of which have not been identified, have a smaller effect on warfarin metabolism. The CYP2C9 gene provides instructions for making an enzyme that breaks down compounds including steroids and fatty acids. The CYP2C9 enzyme also breaks down certain drugs, including warfarin. Several CYP2C9 gene polymorphisms can decrease the activity of the CYP2C9 enzyme and slow the body's metabolism of warfarin. As a result, the drug remains active in the body for a longer period of time, leading to warfarin sensitivity. The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. The VKORC1 enzyme helps turn on (activate) clotting proteins in the pathway that forms blood clots. Warfarin prevents (inhibits) the action of VKORC1 and slows the activation of clotting proteins and clot formation. Certain VKORC1 gene polymorphisms decrease the amount of functional VKORC1 enzyme available to help activate clotting proteins. Individuals develop warfarin sensitivity because less warfarin is needed to inhibit the VKORC1 enzyme, as there is less functional enzyme that needs to be suppressed. While changes in specific genes, particularly CYP2C9 and VKORC1, affect how the body reacts to warfarin, many other factors, including gender, age, weight, diet, and other medications, also play a role in the body's interaction with this drug. | warfarin sensitivity |
Is warfarin sensitivity inherited ? | The polymorphisms associated with this condition are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to result in warfarin sensitivity. However, different polymorphisms affect the activity of warfarin to varying degrees. Additionally, people who have more than one polymorphism in a gene or polymorphisms in multiple genes associated with warfarin sensitivity have a lower tolerance for the drug's effect or take even longer to clear the drug from their body. | warfarin sensitivity |
What are the treatments for warfarin sensitivity ? | These resources address the diagnosis or management of warfarin sensitivity: - Food and Drug Administration Medication Guide - MedlinePlus Drugs & Supplements: Warfarin - My46 Trait Profile - PharmGKB - WarfarinDosing.org These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | warfarin sensitivity |
What is (are) ankylosing spondylitis ? | Ankylosing spondylitis is a form of ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine. This condition is characterized by back pain and stiffness that typically appear in adolescence or early adulthood. Over time, back movement gradually becomes limited as the bones of the spine (vertebrae) fuse together. This progressive bony fusion is called ankylosis. The earliest symptoms of ankylosing spondylitis result from inflammation of the joints between the pelvic bones (the ilia) and the base of the spine (the sacrum). These joints are called sacroiliac joints, and inflammation of these joints is known as sacroiliitis. The inflammation gradually spreads to the joints between the vertebrae, causing a condition called spondylitis. Ankylosing spondylitis can involve other joints as well, including the shoulders, hips, and, less often, the knees. As the disease progresses, it can affect the joints between the spine and ribs, restricting movement of the chest and making it difficult to breathe deeply. People with advanced disease are also more prone to fractures of the vertebrae. Ankylosing spondylitis affects the eyes in up to 40 percent of cases, leading to episodes of eye inflammation called acute iritis. Acute iritis causes eye pain and increased sensitivity to light (photophobia). Rarely, ankylosing spondylitis can also cause serious complications involving the heart, lungs, and nervous system. | ankylosing spondylitis |
How many people are affected by ankylosing spondylitis ? | Ankylosing spondylitis is part of a group of related diseases known as spondyloarthropathies. In the United States, spondyloarthropathies affect 3.5 to 13 per 1,000 people. | ankylosing spondylitis |
What are the genetic changes related to ankylosing spondylitis ? | Ankylosing spondylitis is likely caused by a combination of genetic and environmental factors, most of which have not been identified. However, researchers have found variations in several genes that influence the risk of developing this disorder. The HLA-B gene provides instructions for making a protein that plays an important role in the immune system. The HLA-B gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis. Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the HLA-B gene never develop the disorder. It is not known how HLA-B27 increases the risk of developing ankylosing spondylitis. Variations in several additional genes, including ERAP1, IL1A, and IL23R, have also been associated with ankylosing spondylitis. Although these genes play critical roles in the immune system, it is unclear how variations in these genes affect a person's risk of developing ankylosing spondylitis. Changes in genes that have not yet been identified are also believed to affect the chances of developing ankylosing spondylitis and influence the progression of the disorder. Some of these genes likely play a role in the immune system, while others may have different functions. Researchers are working to identify these genes and clarify their role in ankylosing spondylitis. | ankylosing spondylitis |
Is ankylosing spondylitis inherited ? | Although ankylosing spondylitis can occur in more than one person in a family, it is not a purely genetic disease. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. As a result, inheriting a genetic variation linked with ankylosing spondylitis does not mean that a person will develop the condition, even in families in which more than one family member has the disorder. For example, about 80 percent of children who inherit HLA-B27 from a parent with ankylosing spondylitis do not develop the disorder. | ankylosing spondylitis |
What are the treatments for ankylosing spondylitis ? | These resources address the diagnosis or management of ankylosing spondylitis: - Genetic Testing Registry: Ankylosing spondylitis - MedlinePlus Encyclopedia: Ankylosing Spondylitis - MedlinePlus Encyclopedia: HLA-B27 Antigen These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | ankylosing spondylitis |
What is (are) thiamine-responsive megaloblastic anemia syndrome ? | Thiamine-responsive megaloblastic anemia syndrome is a rare condition characterized by hearing loss, diabetes, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and feet. Individuals with thiamine-responsive megaloblastic anemia syndrome begin to show symptoms of megaloblastic anemia between infancy and adolescence. This syndrome is called "thiamine-responsive" because the anemia can be treated with high doses of vitamin B1 (thiamine). People with thiamine-responsive megaloblastic anemia syndrome develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss) during early childhood. It remains unclear whether thiamine treatment can improve hearing or prevent hearing loss. Diabetes becomes apparent in affected individuals sometime between infancy and adolescence. Although these individuals develop diabetes during childhood, they do not have the form of the disease that develops most often in children, called type 1 (autoimmune) diabetes. People with thiamine-responsive megaloblastic anemia syndrome usually require insulin to treat their diabetes. In some cases, treatment with thiamine can reduce the amount of insulin a person needs. Some individuals with thiamine-responsive megaloblastic anemia syndrome develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Heart and blood vessel (cardiovascular) problems such as heart rhythm abnormalities and heart defects have also been reported in some people with this syndrome. | thiamine-responsive megaloblastic anemia syndrome |
How many people are affected by thiamine-responsive megaloblastic anemia syndrome ? | Thiamine-responsive megaloblastic anemia syndrome has been reported in approximately 30 families worldwide. Its prevalence is unknown. | thiamine-responsive megaloblastic anemia syndrome |
What are the genetic changes related to thiamine-responsive megaloblastic anemia syndrome ? | Mutations in the SLC19A2 gene cause thiamine-responsive megaloblastic anemia syndrome. This gene provides instructions for making a protein called thiamine transporter 1, which transports thiamine into cells. Thiamine is found in many different foods and is important for numerous body functions. Most mutations in the SLC19A2 gene lead to the production of an abnormally short, nonfunctional thiamine transporter 1. Other mutations change single protein building blocks (amino acids) in this protein. All of these mutations prevent thiamine transporter 1 from bringing thiamine into the cell. It remains unclear how the absence of this protein leads to the seemingly unrelated symptoms of megaloblastic anemia, diabetes, and hearing loss. Research suggests that an alternative method for transporting thiamine is present in all the cells of the body, except where blood cells and insulin are formed (in the bone marrow and pancreas, respectively) and cells in the inner ear. | thiamine-responsive megaloblastic anemia syndrome |
Is thiamine-responsive megaloblastic anemia syndrome inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | thiamine-responsive megaloblastic anemia syndrome |
What are the treatments for thiamine-responsive megaloblastic anemia syndrome ? | These resources address the diagnosis or management of thiamine-responsive megaloblastic anemia syndrome: - Gene Review: Gene Review: Thiamine-Responsive Megaloblastic Anemia Syndrome - Genetic Testing Registry: Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness - MedlinePlus Encyclopedia: Optic nerve atrophy - MedlinePlus Encyclopedia: Thiamine These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | thiamine-responsive megaloblastic anemia syndrome |
What is (are) X-linked myotubular myopathy ? | X-linked myotubular myopathy is a condition that primarily affects muscles used for movement (skeletal muscles) and occurs almost exclusively in males. People with this condition have muscle weakness (myopathy) and decreased muscle tone (hypotonia) that are usually evident at birth. The muscle problems in X-linked myotubular myopathy impair the development of motor skills such as sitting, standing, and walking. Affected infants may also have difficulties with feeding due to muscle weakness. Individuals with this condition often do not have the muscle strength to breathe on their own and must be supported with a machine to help them breathe (mechanical ventilation). Some affected individuals need breathing assistance only periodically, typically during sleep, while others require it continuously. People with X-linked myotubular myopathy may also have weakness in the muscles that control eye movement (ophthalmoplegia), weakness in other muscles of the face, and absent reflexes (areflexia). In X-linked myotubular myopathy, muscle weakness often disrupts normal bone development and can lead to fragile bones, an abnormal curvature of the spine (scoliosis), and joint deformities (contractures) of the hips and knees. People with X-linked myotubular myopathy may have a large head with a narrow and elongated face and a high, arched roof of the mouth (palate). They may also have liver disease, recurrent ear and respiratory infections, or seizures. Because of their severe breathing problems, individuals with X-linked myotubular myopathy usually survive only into early childhood; however, some people with this condition have lived into adulthood. X-linked myotubular myopathy is a member of a group of disorders called centronuclear myopathies. In centronuclear myopathies, the nucleus is found at the center of many rod-shaped muscle cells instead of at either end, where it is normally located. | X-linked myotubular myopathy |
How many people are affected by X-linked myotubular myopathy ? | The incidence of X-linked myotubular myopathy is estimated to be 1 in 50,000 newborn males worldwide. | X-linked myotubular myopathy |
What are the genetic changes related to X-linked myotubular myopathy ? | Mutations in the MTM1 gene cause X-linked myotubular myopathy. The MTM1 gene provides instructions for producing an enzyme called myotubularin. Myotubularin is thought to be involved in the development and maintenance of muscle cells. MTM1 gene mutations probably disrupt myotubularin's role in muscle cell development and maintenance, causing muscle weakness and other signs and symptoms of X-linked myotubular myopathy. | X-linked myotubular myopathy |
Is X-linked myotubular myopathy inherited ? | X-linked myotubular myopathy is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In X-linked myotubular myopathy, the affected male inherits one altered copy from his mother in 80 to 90 percent of cases. In the remaining 10 to 20 percent of cases, the disorder results from a new mutation in the gene that occurs during the formation of a parent's reproductive cells (eggs or sperm) or in early embryonic development. Females with one altered copy of the MTM1 gene generally do not experience signs and symptoms of the disorder. In rare cases, however, females who have one altered copy of the MTM1 gene experience some mild muscle weakness. | X-linked myotubular myopathy |
What are the treatments for X-linked myotubular myopathy ? | These resources address the diagnosis or management of X-linked myotubular myopathy: - Gene Review: Gene Review: X-Linked Centronuclear Myopathy - Genetic Testing Registry: Severe X-linked myotubular myopathy These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | X-linked myotubular myopathy |
What is (are) Greig cephalopolysyndactyly syndrome ? | Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, developmental delay, and intellectual disability. | Greig cephalopolysyndactyly syndrome |
How many people are affected by Greig cephalopolysyndactyly syndrome ? | This condition is very rare; its prevalence is unknown. | Greig cephalopolysyndactyly syndrome |
What are the genetic changes related to Greig cephalopolysyndactyly syndrome ? | Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome. The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth. Different genetic changes involving the GLI3 gene can cause Greig cephalopolysyndactyly syndrome. In some cases, the condition results from a chromosomal abnormalitysuch as a large deletion or rearrangement of genetic materialin the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome. | Greig cephalopolysyndactyly syndrome |
Is Greig cephalopolysyndactyly syndrome inherited ? | This condition is inherited in an autosomal dominant pattern, which means one altered or missing copy of the GLI3 gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a gene mutation or chromosomal abnormality from one affected parent. Other cases occur in people with no history of the condition in their family. | Greig cephalopolysyndactyly syndrome |
What are the treatments for Greig cephalopolysyndactyly syndrome ? | These resources address the diagnosis or management of Greig cephalopolysyndactyly syndrome: - Gene Review: Gene Review: Greig Cephalopolysyndactyly Syndrome - Genetic Testing Registry: Greig cephalopolysyndactyly syndrome - MedlinePlus Encyclopedia: Polydactyly - MedlinePlus Encyclopedia: Syndactyly (image) These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Greig cephalopolysyndactyly syndrome |
What is (are) galactosemia ? | Galactosemia is a disorder that affects how the body processes a simple sugar called galactose. A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of galactosemia result from an inability to use galactose to produce energy. Researchers have identified several types of galactosemia. These conditions are each caused by mutations in a particular gene and affect different enzymes involved in breaking down galactose. Classic galactosemia, also known as type I, is the most common and most severe form of the condition. If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and abnormal bleeding. Other serious complications of this condition can include overwhelming bacterial infections (sepsis) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye (cataract), speech difficulties, and intellectual disability. Females with classic galactosemia may develop reproductive problems caused by an early loss of function of the ovaries (premature ovarian insufficiency). Galactosemia type II (also called galactokinase deficiency) and type III (also called galactose epimerase deficiency) cause different patterns of signs and symptoms. Galactosemia type II causes fewer medical problems than the classic type. Affected infants develop cataracts but otherwise experience few long-term complications. The signs and symptoms of galactosemia type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems. | galactosemia |
How many people are affected by galactosemia ? | Classic galactosemia occurs in 1 in 30,000 to 60,000 newborns. Galactosemia type II and type III are less common; type II probably affects fewer than 1 in 100,000 newborns and type III appears to be very rare. | galactosemia |
What are the genetic changes related to galactosemia ? | Mutations in the GALT, GALK1, and GALE genes cause galactosemia. These genes provide instructions for making enzymes that are essential for processing galactose obtained from the diet. These enzymes break down galactose into another simple sugar, glucose, and other molecules that the body can store or use for energy. Mutations in the GALT gene cause classic galactosemia (type I). Most of these genetic changes almost completely eliminate the activity of the enzyme produced from the GALT gene, preventing the normal processing of galactose and resulting in the life-threatening signs and symptoms of this disorder. Another GALT gene mutation, known as the Duarte variant, reduces but does not eliminate the activity of the enzyme. People with the Duarte variant tend to have much milder features of galactosemia. Galactosemia type II results from mutations in the GALK1 gene, while mutations in the GALE gene underlie galactosemia type III. Like the enzyme produced from the GALT gene, the enzymes made from the GALK1 and GALE genes play important roles in processing galactose. A shortage of any of these critical enzymes allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the characteristic features of galactosemia. | galactosemia |
Is galactosemia inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | galactosemia |
What are the treatments for galactosemia ? | These resources address the diagnosis or management of galactosemia: - Baby's First Test: Classic Galactosemia - Baby's First Test: Galactoepimerase Deficiency - Baby's First Test: Galactokinase Deficiency - Gene Review: Gene Review: Classic Galactosemia and Clinical Variant Galactosemia - Gene Review: Gene Review: Duarte Variant Galactosemia - Gene Review: Gene Review: Epimerase Deficiency Galactosemia - Genetic Testing Registry: Galactosemia - MedlinePlus Encyclopedia: Galactose-1-phosphate uridyltransferase - MedlinePlus Encyclopedia: Galactosemia These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | galactosemia |
What is (are) microvillus inclusion disease ? | Microvillus inclusion disease is a condition characterized by chronic, watery, life-threatening diarrhea typically beginning in the first hours to days of life. Rarely, the diarrhea starts around age 3 or 4 months. Food intake increases the frequency of diarrhea. Microvillus inclusion disease prevents the absorption of nutrients from food during digestion, resulting in malnutrition and dehydration. Affected infants often have difficulty gaining weight and growing at the expected rate (failure to thrive), developmental delay, liver and kidney problems, and thinning of the bones (osteoporosis). Some affected individuals develop cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis). In individuals with microvillus inclusion disease, lifelong nutritional support is needed and given through intravenous feedings (parenteral nutrition). Even with nutritional supplementation, most children with microvillus inclusion disease do not survive beyond childhood. A variant of microvillus inclusion disease with milder diarrhea often does not require full-time parenteral nutrition. Individuals with the variant type frequently live past childhood. | microvillus inclusion disease |
How many people are affected by microvillus inclusion disease ? | The prevalence of microvillus inclusion disease is unknown. At least 200 cases have been reported in Europe, although this condition occurs worldwide. | microvillus inclusion disease |
What are the genetic changes related to microvillus inclusion disease ? | Mutations in the MYO5B gene cause microvillus inclusion disease. The MYO5B gene provides instructions for making a protein called myosin Vb. This protein helps to determine the position of various components within cells (cell polarity). Myosin Vb also plays a role in moving components from the cell membrane to the interior of the cell for recycling. MYO5B gene mutations that cause microvillus inclusion disease result in a decrease or absence of myosin Vb function. In cells that line the small intestine (enterocytes), a lack of myosin Vb function changes the cell polarity. As a result, enterocytes cannot properly form structures called microvilli, which normally project like small fingers from the surface of the cells and absorb nutrients and fluids from food as it passes through the intestine. Inside affected enterocytes, small clumps of abnormal microvilli mix with misplaced digestive proteins to form microvillus inclusions, which contribute to the dysfunction of enterocytes. Disorganized enterocytes with poorly formed microvilli reduce the intestine's ability to take in nutrients. The inability to absorb nutrients and fluids during digestion leads to recurrent diarrhea, malnutrition, and dehydration in individuals with microvillus inclusion disease. Some people with the signs and symptoms of microvillus inclusion disease do not have mutations in the MYO5B gene. These cases may be variants of microvillus inclusion disease. Studies suggest that mutations in other genes can cause these cases, but the causes are usually unknown. | microvillus inclusion disease |
Is microvillus inclusion disease inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | microvillus inclusion disease |
What are the treatments for microvillus inclusion disease ? | These resources address the diagnosis or management of microvillus inclusion disease: - Children's Hospital of Pittsburgh - Genetic Testing Registry: Congenital microvillous atrophy - Great Ormond Street Hospital for Children (UK): Intestinal Assessment - International Microvillus Inclusion Disease Patient Registry These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | microvillus inclusion disease |
What is (are) Hermansky-Pudlak syndrome ? | Hermansky-Pudlak syndrome is a disorder characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and white or light-colored hair. People with this disorder have a higher than average risk of skin damage and skin cancers caused by long-term sun exposure. Oculocutaneous albinism reduces pigmentation of the colored part of the eye (iris) and the light-sensitive tissue at the back of the eye (retina). Reduced vision, rapid and involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia) are also common in oculocutaneous albinism. In Hermansky-Pudlak syndrome, these vision problems usually remain stable after early childhood. People with Hermansky-Pudlak syndrome also have problems with blood clotting (coagulation) that lead to easy bruising and prolonged bleeding. Some individuals with Hermansky-Pudlak syndrome develop breathing problems due to a lung disease called pulmonary fibrosis, which causes scar tissue to form in the lungs. The symptoms of pulmonary fibrosis usually appear during an individual's early thirties and rapidly worsen. Individuals with Hermansky-Pudlak syndrome who develop pulmonary fibrosis often do not live for more than a decade after they begin to experience breathing problems. Other, less common features of Hermansky-Pudlak syndrome include inflammation of the large intestine (granulomatous colitis) and kidney failure. There are nine different types of Hermansky-Pudlak syndrome, which can be distinguished by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Little is known about the signs, symptoms, and severity of types 7, 8, and 9. | Hermansky-Pudlak syndrome |
How many people are affected by Hermansky-Pudlak syndrome ? | Hermansky-Pudlak syndrome is a rare disorder in most populations and is estimated to affect 1 in 500,000 to 1,000,000 individuals worldwide. Type 1 is more common in Puerto Rico, particularly in the northwestern part of the island where about 1 in 1,800 people are affected. Type 3 is common in people from central Puerto Rico. Groups of affected individuals have been identified in many other regions, including India, Japan, the United Kingdom, and Western Europe. | Hermansky-Pudlak syndrome |
What are the genetic changes related to Hermansky-Pudlak syndrome ? | At least nine genes are associated with Hermansky-Pudlak syndrome. These genes provide instructions for making proteins that are used to make four distinct protein complexes. These protein complexes play a role in the formation and movement (trafficking) of a group of cell structures called lysosome-related organelles (LROs). LROs are very similar to compartments within the cell called lysosomes, which digest and recycle materials. However, LROs perform specialized functions and are found only in certain cell types. LROs have been identified in pigment-producing cells (melanocytes), blood-clotting cells (platelets), and lung cells. Mutations in the genes associated with Hermansky-Pudlak syndrome prevent the formation of LROs or impair the functioning of these cell structures. In general, mutations in genes that involve the same protein complex cause similar signs and symptoms. People with this syndrome have oculocutaneous albinism because the LROs within melanocytes cannot produce and distribute the substance that gives skin, hair, and eyes their color (melanin). Bleeding problems are caused by the absence of LROs within platelets, which affects the ability of platelets to stick together and form a blood clot. Mutations in some of the genes that cause Hermansky-Pudlak syndrome affect the normal functioning of LROs in lung cells, leading to pulmonary fibrosis. Mutations in the HPS1 gene cause approximately 75 percent of the Hermansky-Pudlak syndrome cases from Puerto Rico. About 45 percent of affected individuals from other populations have mutations in the HPS1 gene. Mutations in the HPS3 gene are found in about 25 percent of affected people from Puerto Rico and in approximately 20 percent of affected individuals from other areas. The other genes associated with Hermansky-Pudlak syndrome each account for a small percentage of cases of this condition. In some people with Hermansky-Pudlak syndrome, the genetic cause of the disorder is unknown. | Hermansky-Pudlak syndrome |
Is Hermansky-Pudlak syndrome inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | Hermansky-Pudlak syndrome |
What are the treatments for Hermansky-Pudlak syndrome ? | These resources address the diagnosis or management of Hermansky-Pudlak syndrome: - Gene Review: Gene Review: Hermansky-Pudlak Syndrome - Genetic Testing Registry: Hermansky-Pudlak syndrome - Genetic Testing Registry: Hermansky-Pudlak syndrome 1 - MedlinePlus Encyclopedia: Albinism - MedlinePlus Encyclopedia: Colitis These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Hermansky-Pudlak syndrome |
What is (are) incontinentia pigmenti ? | Incontinentia pigmenti is a condition that can affect many body systems, particularly the skin. This condition occurs much more often in females than in males. Incontinentia pigmenti is characterized by skin abnormalities that evolve throughout childhood and young adulthood. Many affected infants have a blistering rash at birth and in early infancy, which heals and is followed by the development of wart-like skin growths. In early childhood, the skin develops grey or brown patches (hyperpigmentation) that occur in a swirled pattern. These patches fade with time, and adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs. Other signs and symptoms of incontinentia pigmenti can include hair loss (alopecia) affecting the scalp and other parts of the body, dental abnormalities (such as small teeth or few teeth), eye abnormalities that can lead to vision loss, and lined or pitted fingernails and toenails. Most people with incontinentia pigmenti have normal intelligence; however, this condition may affect the brain. Associated problems can include delayed development or intellectual disability, seizures, and other neurological problems. | incontinentia pigmenti |
How many people are affected by incontinentia pigmenti ? | Incontinentia pigmenti is an uncommon disorder. Between 900 and 1,200 affected individuals have been reported in the scientific literature. Most of these individuals are female, but several dozen males with incontinentia pigmenti have also been identified. | incontinentia pigmenti |
What are the genetic changes related to incontinentia pigmenti ? | Mutations in the IKBKG gene cause incontinentia pigmenti. The IKBKG gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that helps protect cells from self-destructing (undergoing apoptosis) in response to certain signals. About 80 percent of affected individuals have a mutation that deletes some genetic material from the IKBKG gene. This deletion probably leads to the production of an abnormally small, nonfunctional version of the IKBKG protein. Other people with incontinentia pigmenti have mutations that prevent the production of any IKBKG protein. Without this protein, nuclear factor-kappa-B is not regulated properly, and cells are more sensitive to signals that trigger them to self-destruct. Researchers believe that this abnormal cell death leads to the signs and symptoms of incontinentia pigmenti. | incontinentia pigmenti |
Is incontinentia pigmenti inherited ? | This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of IKBKG protein and other cells produce none. The resulting imbalance in cells producing this protein leads to the signs and symptoms of incontinentia pigmenti. In males (who have only one X chromosome), most IKBKG mutations result in a total loss of the IKBKG protein. A lack of this protein appears to be lethal early in development, so few males are born with incontinentia pigmenti. Affected males who survive may have an IKBKG mutation with relatively mild effects, an IKBKG mutation in only some of the body's cells (mosaicism), or an extra copy of the X chromosome in each cell. Some people with incontinentia pigmenti inherit an IKBKG mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. | incontinentia pigmenti |
What are the treatments for incontinentia pigmenti ? | These resources address the diagnosis or management of incontinentia pigmenti: - Gene Review: Gene Review: Incontinentia Pigmenti - Genetic Testing Registry: Incontinentia pigmenti syndrome - MedlinePlus Encyclopedia: Incontinentia Pigmenti Syndrome These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | incontinentia pigmenti |
What is (are) Cornelia de Lange syndrome ? | Cornelia de Lange syndrome is a developmental disorder that affects many parts of the body. The features of this disorder vary widely among affected individuals and range from relatively mild to severe. Cornelia de Lange syndrome is characterized by slow growth before and after birth leading to short stature; intellectual disability that is usually moderate to severe; and abnormalities of bones in the arms, hands, and fingers. Most people with Cornelia de Lange syndrome also have distinctive facial features, including arched eyebrows that often meet in the middle (synophrys), long eyelashes, low-set ears, small and widely spaced teeth, and a small and upturned nose. Many affected individuals also have behavior problems similar to autism, a developmental condition that affects communication and social interaction. Additional signs and symptoms of Cornelia de Lange syndrome can include excessive body hair (hypertrichosis), an unusually small head (microcephaly), hearing loss, and problems with the digestive tract. Some people with this condition are born with an opening in the roof of the mouth called a cleft palate. Seizures, heart defects, and eye problems have also been reported in people with this condition. | Cornelia de Lange syndrome |
How many people are affected by Cornelia de Lange syndrome ? | Although the exact incidence is unknown, Cornelia de Lange syndrome likely affects 1 in 10,000 to 30,000 newborns. The condition is probably underdiagnosed because affected individuals with mild or uncommon features may never be recognized as having Cornelia de Lange syndrome. | Cornelia de Lange syndrome |
What are the genetic changes related to Cornelia de Lange syndrome ? | Cornelia de Lange syndrome can result from mutations in at least five genes: NIPBL, SMC1A, HDAC8, RAD21, and SMC3. Mutations in the NIPBL gene have been identified in more than half of all people with this condition; mutations in the other genes are much less common. The proteins produced from all five genes contribute to the structure or function of the cohesin complex, a group of proteins with an important role in directing development before birth. Within cells, the cohesin complex helps regulate the structure and organization of chromosomes, stabilize cells' genetic information, and repair damaged DNA. The cohesin complex also regulates the activity of certain genes that guide the development of limbs, face, and other parts of the body. Mutations in the NIPBL, SMC1A, HDAC8, RAD21, and SMC3 genes cause Cornelia de Lange syndrome by impairing the function of the cohesin complex, which disrupts gene regulation during critical stages of early development. The features of Cornelia de Lange syndrome vary widely, and the severity of the disorder can differ even in individuals with the same gene mutation. Researchers suspect that additional genetic or environmental factors may be important for determining the specific signs and symptoms in each individual. In general, SMC1A, RAD21, and SMC3 gene mutations cause milder signs and symptoms than NIPBL gene mutations. Mutations in the HDAC8 gene cause a somewhat different set of features, including delayed closure of the "soft spot" on the head (the anterior fontanelle) in infancy, widely spaced eyes, and dental abnormalities. Like affected individuals with NIPBL gene mutations, those with HDAC8 gene mutations may have significant intellectual disability. In about 30 percent of cases, the cause of Cornelia de Lange syndrome is unknown. Researchers are looking for additional changes in the five known genes, as well as mutations in other genes, that may cause this condition. | Cornelia de Lange syndrome |
Is Cornelia de Lange syndrome inherited ? | When Cornelia de Lange syndrome is caused by mutations in the NIPBL, RAD21, or SMC3 gene, the condition is considered to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new gene mutations and occur in people with no history of the condition in their family. When Cornelia de Lange syndrome is caused by mutations in the HDAC8 or SMC1A gene, the condition has an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. Studies of X-linked Cornelia de Lange syndrome indicate that one copy of the altered gene in each cell may be sufficient to cause the condition. Unlike X-linked recessive conditions, in which males are more frequently affected or experience more severe symptoms than females, X-linked dominant Cornelia de Lange syndrome appears to affect males and females similarly. Most cases result from new mutations in the HDAC8 or SMC1A gene and occur in people with no history of the condition in their family. | Cornelia de Lange syndrome |
What are the treatments for Cornelia de Lange syndrome ? | These resources address the diagnosis or management of Cornelia de Lange syndrome: - Gene Review: Gene Review: Cornelia de Lange Syndrome - Genetic Testing Registry: De Lange syndrome - MedlinePlus Encyclopedia: Autism - MedlinePlus Encyclopedia: Microcephaly These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Cornelia de Lange syndrome |
What is (are) autoimmune polyglandular syndrome, type 1 ? | Autoimmune polyglandular syndrome, type 1 is an inherited condition that affects many of the body's organs. It is one of many autoimmune diseases, which are disorders that occur when the immune system malfunctions and attacks the body's tissues and organs by mistake. In most cases, the signs and symptoms of autoimmune polyglandular syndrome, type 1 begin in childhood or adolescence. This condition is characterized by three specific features: mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. Affected individuals typically have at least two of these features, and many have all three. Mucocutaneous candidiasis is a fungal infection that affects the skin and mucous membranes, such as the moist lining of the nose and mouth. In children with autoimmune polyglandular syndrome, type 1, these infections last a long time and tend to recur. Many affected children also develop hypoparathyroidism, which is a malfunction of the parathyroid glands. These glands secrete a hormone that regulates the body's use of calcium and phosphorus. Hypoparathyroidism can cause a tingling sensation in the lips, fingers, and toes; muscle pain and cramping; weakness; and fatigue. The third major feature, Addison disease, results from a malfunction of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and changes in skin coloring. Autoimmune polyglandular syndrome, type 1 can cause a variety of additional signs and symptoms, although they occur less often. Complications of this disorder can affect the skin and nails, the gonads (ovaries and testicles), the eyes, a butterfly-shaped gland at the base of the neck called the thyroid, and the digestive system. Type 1 diabetes also occurs in some patients with this condition. | autoimmune polyglandular syndrome, type 1 |
How many people are affected by autoimmune polyglandular syndrome, type 1 ? | Autoimmune polyglandular syndrome, type 1 is thought to be a rare condition, with about 500 cases reported worldwide. This condition occurs more frequently in certain populations, including Iranian Jews, Sardinians, and Finns. | autoimmune polyglandular syndrome, type 1 |
What are the genetic changes related to autoimmune polyglandular syndrome, type 1 ? | Mutations in the AIRE gene cause autoimmune polyglandular syndrome, type 1. The AIRE gene provides instructions for making a protein called the autoimmune regulator. As its name suggests, this protein plays a critical role in regulating certain aspects of immune system function. Specifically, it helps the body distinguish its own proteins and cells from those of foreign invaders (such as bacteria and viruses). This distinction is critical because to remain healthy, a person's immune system must be able to identify and destroy potentially harmful invaders while sparing the body's normal tissues. Mutations in the AIRE gene reduce or eliminate the function of the autoimmune regulator protein. Without enough of this protein, the immune system can turn against itself and attack the body's own organs. This reaction, which is known as autoimmunity, results in inflammation and can damage otherwise healthy cells and tissues. Damage to the adrenal glands, parathyroid glands, and other organs underlies many of the major features of autoimmune polyglandular syndrome, type 1. It remains unclear why people with this condition tend to get candidiasis infections. Although most of the characteristic features of autoimmune polyglandular syndrome, type 1 result from mutations in the AIRE gene, researchers believe that variations in other genes may help explain why the signs and symptoms of this condition can vary among affected individuals. | autoimmune polyglandular syndrome, type 1 |
Is autoimmune polyglandular syndrome, type 1 inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | autoimmune polyglandular syndrome, type 1 |
What are the treatments for autoimmune polyglandular syndrome, type 1 ? | These resources address the diagnosis or management of autoimmune polyglandular syndrome, type 1: - Genetic Testing Registry: Autoimmune polyglandular syndrome type 1, autosomal dominant - Genetic Testing Registry: Autoimmune polyglandular syndrome type 1, with reversible metaphyseal dysplasia - Genetic Testing Registry: Polyglandular autoimmune syndrome, type 1 - MedlinePlus Encyclopedia: Addison's Disease - MedlinePlus Encyclopedia: Autoimmune Disorders - MedlinePlus Encyclopedia: Cutaneous Candidiasis - MedlinePlus Encyclopedia: Hypoparathyroidism These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | autoimmune polyglandular syndrome, type 1 |
What is (are) progressive familial intrahepatic cholestasis ? | Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals. Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly). There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause. In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood. The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma. Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3. | progressive familial intrahepatic cholestasis |
How many people are affected by progressive familial intrahepatic cholestasis ? | PFIC is estimated to affect 1 in 50,000 to 100,000 people worldwide. PFIC type 1 is much more common in the Inuit population of Greenland and the Old Order Amish population of the United States. | progressive familial intrahepatic cholestasis |
What are the genetic changes related to progressive familial intrahepatic cholestasis ? | Mutations in the ATP8B1, ABCB11, and ABCB4 genes can cause PFIC. ATP8B1 gene mutations cause PFIC1. The ATP8B1 gene provides instructions for making a protein that helps to maintain an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. In its role in maintaining bile acid homeostasis, some researchers believe that the ATP8B1 protein is involved in moving certain fats across cell membranes. Mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells, damaging these cells and causing liver disease. The ATP8B1 protein is found throughout the body, but it is unclear how a lack of this protein causes short stature, deafness, and other signs and symptoms of PFIC1. Mutations in the ABCB11 gene are responsible for PFIC2. The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells. Mutations in the ABCB11 gene result in the buildup of bile salts in liver cells, damaging these cells and causing liver disease. ABCB4 gene mutations cause PFIC3. The ABCB4 gene provides instructions for making a protein that moves certain fats called phospholipids across cell membranes. Outside liver cells, phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Mutations in the ABCB4 gene lead to a lack of phospholipids available to bind to bile acids. A buildup of free bile acids damages liver cells and leads to liver disease. Some people with PFIC do not have a mutation in the ATP8B1, ABCB11, or ABCB4 gene. In these cases, the cause of the condition is unknown. | progressive familial intrahepatic cholestasis |
Is progressive familial intrahepatic cholestasis inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | progressive familial intrahepatic cholestasis |
What are the treatments for progressive familial intrahepatic cholestasis ? | These resources address the diagnosis or management of progressive familial intrahepatic cholestasis: - Gene Review: Gene Review: ATP8B1 Deficiency - Genetic Testing Registry: Progressive familial intrahepatic cholestasis 2 - Genetic Testing Registry: Progressive familial intrahepatic cholestasis 3 - Genetic Testing Registry: Progressive intrahepatic cholestasis - MedlinePlus Encyclopedia: Cholestasis - MedlinePlus Encyclopedia: Hepatocellular Carcinoma These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | progressive familial intrahepatic cholestasis |
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