MSUD

Patients with the autosomal recessive disorder MSUD have a defect of the branched-chain ketoacid dehydrogenase enzyme complex because of mutations in one of the genes encoding one of the subunits of the complex. This enzyme is catalyzing a common step in the degradation of the branched chain amino acids leucine, isoleucine and valine. The disorder can present in different ways, but the main clinical problem is neurological damage and high mortality. In Norway we have several patients with the intermittent phenotype. The project is a cooperation between Section for Biochemical Genetics, Institute of Clinical Biochemistry and Department of Pediatrics. The aim of the project is to characterize the mutational spectrum of Norwegian patients with intermittent MSUD, and to elucidate the way the mutations cause disease. It has also been proposed that the enzyme has additional functions, because the E2-sububit is found in close association with mitochondrial DNA. Another aim of the project is to elucidate the functional significance of this association for mitochondrial processes by studying human fibroblasts as well as animal models.