Enzyme activity in classical and variant forms of maple syrup urine disease

The branched-chain keto acid decarboxylase activity has been determined in skinfibroblasts grown from six subjects with classical maple syrup urine disease and six with variant forms of the disease. The level of activity in the skin fibroblasts reflects the ability of the individual to degrade the amino acids, thus providing an index of the severity of the disease. Observations on sibling pairs indicate that the level of enzyme activity and the severity of the disease are genetically determined. A 3 grade classification is proposed based on tolerance for dietary protein. The metabolic defect in all instances involved the three branched-chain amino acids, providing further support for the concept that this degradative step is under the control of a single gene.