Characterization of a point mutation in the pyruvate dehydrogenase E1α gene from two boys with primary lactic acidaemia

We report here a novel mutation in the codon for amino acid 263 resulting in the change from arginine to glutamine in the pyruvate dehydrogenase (PDH) E1α gene, in two boys with primary lactic acidaemia, from independent families. The mutation changes an amino acid located between the two serine residues which are the sites of phosphorylation of the subunit protein. In one family, the mutation wasde novo and in the other it was transmitted from mother to son. The amino acid substitution may affect function of the PDH complex via phosphorylation and dephosphorylation of the E1α subunit. Derangement in the regulation of activity of the PDH complex may explain the primary lactic acidaemia in the patients.