Academic literature on the topic 'Branched-chain alpha-ketoacid dehydrogenase (BCKD) complex'

Abstract Maple syrup urine disease (MSUD) is a heterogeneous genetic disorder resulting from over 50 known mutations that impair the mitochondrial branched-chain a-ketoacid dehydrogenase (BCKD) complex. The components of the BCKD complex include E1, a decarboxylase; E2, an acyl transferase; and E3, a lipomide dehydrogenase (dihydrolipoyl dehydrogenase). The defect in this multienzyme complex results in accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine and their respective a-ketoacids (BCKAs) in body fluids (Fig. 38–1). Maple syrup urine disease is inherited as an autosomal recessive trait. Its incidence varies with the population studied, from 1/760 in selective screening of an inbred Mennonite group to 1/290,000 in a New England newborn screening program. Molecular mutation analysis has not revealed a strong genotype-phenotype correlation to date. Numerous variant forms of MSUD resulting in a spectrum of BCKD insufficiency (3% to 40% normal) have been reported. The clinical outcome appears to be associated with the age at diagnosis, the degree of enzyme impairment, the time at which diet therapy is begun, and the degree of metabolic control. Five clinical and biochemical phenotypes have been reported and used based on clinical presentation and therapeutic responses to thiamin observed in patients.