Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: Dihydrolipoamide acetyltransferase (E2) 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 E1α subunit of the complex. Mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 core component of the complex, have not been described previously. We report two unrelated patients with pyruvate dehydrogenase deficiency caused by defects in the E2 subunit. Both patients are less severely affected than typical patients with E1α 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. Ann Neurol 2005;58:234–241