Characterization of a point mutation in the pyruvate dehydrogenase E1 alpha gene from two boys with primary lactic acidaemia

J Inherit Metab Dis. 1994;17(2):189-95. doi: 10.1007/BF00711616.


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) E1 alpha 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 was de 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 E1 alpha subunit. Derangement in the regulation of activity of the PDH complex may explain the primary lactic acidaemia in the patients.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / enzymology
  • Acidosis, Lactic / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Point Mutation*
  • Polymerase Chain Reaction
  • Pyruvate Dehydrogenase Complex / genetics*
  • Restriction Mapping


  • Oligonucleotide Probes
  • Pyruvate Dehydrogenase Complex