You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information.
What is Megaloblastic anemia resistant to treatment is seen with and explain in detail?
Ans. c (Orotic aciduria) (Ref. Harrison's Principles of Internal Medicine 17th ed., 651, 2449)Paragraph from Harrison's medicine 17th/p. 2449Orotic Aciduria# Hereditary orotic aciduria is caused by mutations in a bifunctional enzyme, uridine-S'-monophosphate (UMP) synthase, which converts orotic acid to UMP in the de novo synthesis pathway.# It is characterized by: hypochromic megaloblastic anemia that is unresponsive to vitamin B12 and folic acid, growth retardation, and neurologic abnormalities.# Increased excretion of orotic acid causes crystalluria and obstructive uropathy.# Replacement of uridine (100-200 mg/kg per day) corrects the anemia, reduces orotic acid excretion, and improves the other sequelae of the disorder.OROTIC ACIDURIA# It is a rare disorder of pyrimidine metabolism.# Two enzymatic functions are defective in this disorder:- Orotidine-5-prime-pyrophosphorylase and- Decarboxylase for orotidine-5-prime-phosphate.# Characterised by- Hypochromic anemia with megaloblastic changes in bone marrow not responding to folic acid or vit.BI2,- Leukopenia,- Retarded growth, and- Urinary excretion of orotic acid# The phenotypic features of orotic aciduria:# Megaloblastic anemia that is unresponsive to vitamin B12 and folic acid.# Hypochromic, microcytic circulating erythrocytes that persist with administration of iron or pyridoxine.# Large amounts of orotic acid in the urine.# Correction of anemia and i in orotic acid excretion on uridylic acid and cytidylic acid administration.MEGALOBLASTIC ANEMIA: TREATMENTTreatment of Cobalamin Deficiency# Lifelong regular cobalamin injections.# Cobalamin should be given routinely to all patients who have had a total gastrectomy or ileal resection.# Patients who have undergone gastric reduction for control of obesity or who are receiving long-term treatment with proton pump inhibitors should be screened and, if necessary, given cobalamin replacement.# Replenishment of body stores should be complete with six lOOOmg IM inj of hydroxocobalamin at 3-7 day intervals.# For maintenance therapy, 1000 mg hydroxocobalamin IM once every 3 months is satisfactory.# Sublingual therapy has also been proposed for those in whom injections are difficult.Treatment of Folate Deficiency# Oral doses of 5-15 mg folic acid daily for about 4 months# Before large doses of folic acid are given, cobalamin deficiency must be excluded and, if present, corrected, other- wise cobalamin neuropathy may develop, despite a response of the anemia of cobalamin deficiency to folate therapy.# Long-term folic acid therapy is required in chronic dialysis or hemolytic anemias, in gluten-induced enteropathy.