A case of PDH-E1 alpha mosaicism in a male patient with severe metabolic lactic acidosis.

We have characterized a novel mutation in a male patient that affects the coding sequence of PDH-E1 alpha gene and changes arginine-141 to a leucine. This nucleotide substitution was found in about 75% of the studied DNA (fibroblasts, liver and muscle), a scenario that would indicate a case of E1 alpha mosaicism in a male patient. When the mutant E1 alpha protein was expressed in human skin fibroblasts with zero endogenous pyruvate dehydrogenase complex activity and E1 alpha protein expression, no significant restoration of activity was recorded, in contrast to the wild-type cDNA. even though both wild-type and mutant protein levels were comparable. We concluded that the R141L mutation is a severe one and that it must have occurred in one of the E1 alpha alleles during early embryogenesis.