Molecular genetic characterization of maple syrup urine disease in European families

Maple syrup urine disease results from defects in the branched chain alpha-ketoacid dehydrogenase complex. Cells from seven German, three Turkish, and two Italian families including five consanguineous matings were analyzed for the causative mutations. Enzyme assays were used to confirm the initial clinical diagnosis of all probands. Immunoblots of mitochondrial proteins from these probands revealed reduced expression of the E1 alpha and beta proteins of the complex. Previous studies showed that interaction of alpha and beta was necessary to stabilize both proteins so that defects in either protein can result in decreased presence of both. The E1 alpha Y393N mutation common in the Mennonite population that results in diminished amounts of both alpha and beta proteins was not the cause of the reduction in these European patients.