Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression

Abstract Maple syrup urine disease [MSUD] is a rare inborn error of metabolism inherited as an autosomal recessive trait through mutations in any of three different genes that encode components of the branched chain α-ketoacid dehydrogenase [BCKD] complex. In this work, the genotype of affected individuals was correlated with their clinical histories. These individuals were diagnosed and followed in a single centralized clinic, and their molecular genetic characterization was done by one laboratory. Three individuals had mutant alleles in the gene for the E1α component, five had mutations in the gene for E1β, and three had mutations in the gene for E2. The results emphasize the diversity of the molecular and clinical presentations for individuals with MSUD and support the complexity of diseases termed “single gene traits.” Of primary importance is early identification of at risk infants through newborn screening programs to minimize many of the complications associated with this protein intolerance. Attention to abnormal neurological signs in the neonate or evidence of neurological decompensation in older infants and children by a centralized medical management team minimizes permanent brain damage and improves survival.