branched chain ketoaciduria
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ma·ple syr·up u·rine dis·ease[MIM*248600]
an inborn error of metabolism caused by defective oxidative decarboxylation of α-keto acids of leucine, isoleucine, and valine; these branched-chain amino acids are present in the blood and urine in high concentrations; manifestations of disease include feeding difficulties, physical and mental retardation, and a urine odor similar to that of maple syrup; neonatal death is common. Autosomal recessive inheritance, caused by mutation in the E1, E2 or E3 subunit of the branched-chain α-keto acid dehydrogenase gene (BCKDH) on 19q. There are various forms differentiated by the subunit of BCKDH mutated.
Frequency General population 1:200,000; in Pennsylvania Mennonites of German descent 1:176
Pathogenesis The defect in oxidative decarboxylation of branched chain amino acids—BCAA—valine, leucine and isoleucine results in accumulation of BCAA
Lab Increased BCAA, decreased threonine, serine, alanine in urine and serum, positive dinitro-phenylhydrazine test for alpha-keto amino acids, which form insoluble hydrazines
Management Dietary decrease of BCAA, plus dietary overload—20-fold excess of thiamine
Prognosis Mortality was 100%, often due to intercurrent infection; with BCAA-free infant formulas, the survival is ±100% and mental retardation completely preventable; since acute decompensation by BCAA and BCKA is due to a breakdown of endogenous proteins resulting in metabolic acidosis, ketosis, anorexia, emesis and potentially fatal encephalopathy, patients may respond to parenteral solutions of BCAA-free amino acids