A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)

Abstract

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disease caused by mutations in the BCKDHA, BCKDHB, DBT and DLD genes, which encode the E1α, E1β, E2 and E3 subunits of the branched chain α ketoacid dehydrogenase (BCKD) complex, respectively. This complex is involved in the metabolism of branched-chain amino acids. In this study, we analyzed the DNA sequences of BCKDHA and BCKDHB genes in an infant who suffered from MSUD and died at the age of 6 months. We found a new missense mutation in exon 5 of BCKDHB gene (c.508C>T). The heterozygosity of the parents for the mentioned nucleotide change was confirmed by direct sequence analysis of the corresponding segment. Another missense mutation has been found in the same codon previously and shown by in silico analyses to be deleterious. This report provides further evidence that this amino acid change can cause classic MSUD.

Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population

“…Without timely intervention, the disease progresses rapidly, and the mortality and disability rate are very high. According to the phenotype, MSUD can be divided into 5 types 1 : classic, intermediate, intermittent, thiamine-responsive and dihydrolipoylamide dehydrogenase (E3) deficiency. The classic type is the most common and severe type in the neonatal period, accounting for 75% affected infants.…”

Silico analysis of a novel mutation c.550delT in a Chinese patient with maple syrup urine disease

“…BCKD is composed of three catalytic components: a branched‐chain α‐keto acid decarboxylase (E1) formed by two E1α and two E1β subunits, a dihydrolipoyl transacylase (E2), and a dihydrolipoamide dehydrogenase (E3), encoded by the BCKDHA , BCKDHB , DBT, and DLD genes, respectively . The dysfunction of BCKD complex may cause by mutations in these four genes and then inducing the occurrence of MSUD …”

“…4,5 The dysfunction of BCKD complex may cause by mutations in these four genes and then inducing the occurrence of MSUD. [6][7][8] Based on clinical presentation onset age and residual BCKD complex activity, MUSD can be divided into five forms: classic, intermediate, intermittent, thiamine responsive, and E3 deficient. 9,10 Approximately 75% of affected individuals has the classic form with less than 2% residual BCKD complex activity and exhibits the most serious phenotype.…”