A case of PDH-E-1 alpha mosaicism in a male patient with severe metabolic lactic acidosis

We have characterized a novel mutation in a male patient that affects the c oding sequence of PDH-E(1)alpha gene and changes arginine-141 to a leucine. This nucleotide substitution was found in about 75% of the studied DNA (fi broblasts, liver and muscle), a scenario that would indicate a case of E(1) alpha mosaicism in a male patient. When the mutant E(1)alpha protein was ex pressed in human skin fibroblasts with zero endogenous pyruvate dehydrogena se complex activity and E(1)alpha protein expression, no significant restor ation of activity was recorded, in contrast to the wild-type cDNA, even tho ugh 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 o ne of the E(1)alpha alleles during early embryogenesis.