• maple syrup urine disease type II

This report describes maple syrup urine disease, type II, a subtype of maple syrup urine disease (MSUD); MSUD type II exhibits autosomal recessive inheritance. The human gene implicated in this disease is DBT, which encodes a subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKD), an inner-mitochondrial enzyme complex involved in the breakdown of the branched-chain amino acids isoleucine, leucine, and valine. There is a single orthologous gene in Drosophila, Dbct, for which an engineered null mutation, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and other genetic reagents have been generated.

The human DBT gene has not been introduced into flies.

Animals homozygous for a null mutation of Dbct survive to the pupal stage; at the larval stage multiple MSUD phenotypes are recapitulated, including aberrant branched-chain amino acid accumulation, developmental defects, poor mobile behavior and disrupted L-glutamate homeostasis. Neural abnormalities in the brain and in the developing eye are observed. Administration of the drug Metformin ameliorates many of the observed phenotypes.

[updated Oct. 2020 by FlyBase; FBrf0222196]