Molecular Identification of BCKDHB & DBT Gene Mutations in Maple Syrup Urine Disease in Egyptian Infants

Abstract

Maple syrup urine disease (MSUD, OMIM #248600) is an autosomal inborn disorder, triggered by a mutation in BCKDHA, BCKDHB and DBT genes that encoding E1α, E1β and E2 of branched chain ketoacid dehydrogenase (BCKDH) complex. This multi-enzyme complex involves in the metabolism of branched chain amino acids (BCAAs): leucine, isoleucine and valine via the oxidative decaboylation. The deficiency of BCKDH causes the accumulation of BCAAs and their crossponding α- ketoacids in the blood leading to brain encephalopathy. The worldwide incidence of MSUD is estimated 1:185000 and the rate elevated in population characterized by consanguineous marriage, but the incidence in Egyptain population has not yet been reported. The MSUD genotype is determined according to the affected loci: type IA for the BCKDHA gene (E1α subunit); type IB for the BCKDHB gene (E1β subunit) and type II for the DBT gene (E2 subunit). MSUD patients are categorized based on the severity of symptoms into classic form which represents 75% of patients and is considred the