Primary human fibroblasts from a maple syrup urine disease patient undergo apoptosis following exposure to physiological concentrations of branched chain amino acids.

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-ketoacid dehydrogenase. We have recently found that MSUD neurodegeneration may result, at least in part, from apoptosis triggered by branched chain amino acids and their alpha-ketoacid derivatives. In the present study, we investigated the sensitivity of MSUD fibroblasts to defined mixtures of MSUD metabolites. Defined combinations of MSUD metabolites, at levels comparable to those in MSUD patients, triggered cell death in skin fibroblasts from a MSUD patient, while control fibroblasts were resistant. The mechanism of cell death was confirmed as apoptosis by in situ end labeling.