cervical vertebrae. Upper and lower respiratory tract infections can be frequent. Developmental delay may become apparent by age 1–2 years, with a maximum functional age of 2–4 years. Progressive deterioration follows. Most children develop limited language capabilities. Death usually occurs by age 10. Genetics Children with Hurler Syndrome carry two defective copies of the IDUA gene, which has been mapped to the 4p16.3 site on chromosome 4. This is the gene which encodes for the protein iduronidase. , more than 201 different mutations in the IDUA gene have been shown to cause MPS I. Because Hurler syndrome is an autosomal recessive disorder, affected persons have two nonworking copies of the gene. A person born with one normal copy and one defective copy is called a carrier. They will produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease. Mechanisms The IDUA gene is responsible for encoding an enzyme called alpha-L-iduronidase. Through hydrolysis, alpha-L-iduronidase is responsible for breaking down a molecule called unsulfated alpha-L-iduronic acid. This is a uronic acid found in the GAGs dermatan sulfate and heparan sulfate. The alpha-L-iduronidase enzyme is located in lysosomes. Without sufficient enzymatic function, these GAGs cannot be digested properly. Diagnosis Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders. Classification All members of the mucopolysaccharidosis family are also lysosomal storage diseases. Mucopolysaccharidosis type I (MPS I) is divided into three subtypes based on severity of symptoms. All three types result the absence or decreased functioning of the same enzyme. MPS-IH (Hurler syndrome) is the most severe of the MPS I subtypes. The other two types are MPS-IS (Scheie syndrome) and MPS-IHS (Hurler–Scheie syndrome). Because of the substantial overlap between Hurler syndrome, Hurler–Scheie syndrome, and Scheie syndrome, some sources consider