کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5518547 | 1543975 | 2017 | 4 صفحه PDF | دانلود رایگان |
Isovaleric acidemia (IVA) is an organic acid disease caused by a deficiency of isovaleryl-CoA dehydrogenase. Deficiency of this enzyme leads to accumulation of organic acids, such as isovalerylcarnitine and isovalerylglycine. The proposed IVA treatments include leucine restriction and l-carnitine and/or glycine supplementation, which convert isovaleric acid into non-toxic isovalerylcarnitine and isovalerylglycine, respectively. We examined the therapeutic response using the leucine load test and performed a 10-year follow-up in the patient.MethodsWe evaluated the patient with IVA beginning at 5Â years of age, when he presented with a mild to intermediate metabolic phenotype. Ammonia, free carnitine, isovalerylcarnitine, and isovalerylglycine were analyzed in the urine and blood after a meal consisting of 1600Â mg leucine with glycine alone (250Â mg/kg/day), l-carnitine alone (100Â mg/kg/day), or both glycine and l-carnitine for four days each.Results(Leucine load test) Three hours after the meal, serum ammonia levels increased most dramatically with glycine treatment alone, then with both in combination, and least with l-carnitine alone. Urinary isovalerylglycine levels increased 2-fold more with glycine supplementation than those following supplementation with both agents or with l-carnitine alone. Treatment with both agents resulted in a gradual increase in urinary acylcarnitine levels during the 6-h period following the leucine load, reaching concentrations comparable to those observed with l-carnitine alone. (Clinical course) After initiation of both glycine (200Â mg/kg/day) and l-carnitine (100Â mg/kg/day) supplementation at 5Â years of age, doses were gradually reduced to 111.7Â mg/kg/day and 55.8Â mg/kg/day, respectively, at 15Â years of age. His mind and body had developed without any sequelae.DiscussionWe concluded that l-carnitine conjugated isovaleric acid earlier than glycine. Additionally, during the 10-year follow-up period, the patient displayed no clinical deterioration.
Journal: Molecular Genetics and Metabolism Reports - Volume 11, June 2017, Pages 2-5