Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency.

[pyruvate dehydrogenase deficiency]

Pyruvate dehydrogenase deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood . Most cases are caused by mutations in the X-linked gene for the E 1 alpha subunit of the complex . Mutations in DLAT , the gene encoding dihydrolipoamide acetyltransferase , the E 2 core component of the complex , have not been described previously . We report two unrelated patients with pyruvate dehydrogenase deficiency caused by defects in the E 2 subunit . Both patients are less severely affected than typical patients with E 1 alpha mutations and both have survived well into childhood . Episodic dystonia was the major neurological manifestation , with other more common features of pyruvate dehydrogenase deficiency , such as hypotonia and ataxia , being less prominent . The patients had neuroradiological evidence of discrete lesions restricted to the globus pallidus , and both are homozygous for different mutations in the DLAT gene . The clinical presentation and neuroradiological findings are not typical of pyruvate dehydrogenase deficiency and extend the clinical and mutational spectrum of this condition .