PYRUVATE-DEHYDROGENASE DEFICIENCY - CLINICAL AND BIOCHEMICAL-DIAGNOSIS

A female neonate with pyruvate dehydrogenase (PDH) deficiency is prese nted with clinical, radiologic, biochemical, neuropathologic, and mole cular genetic data. She was dysmorphic, with a high forehead, low-set ears, thin upper lip, upturned nose, and rhizomelic limbs. Cranial MRI revealed severe cortical atrophy, ventricular dilatation, and corpus callosum agenesis. Pyruvate and lactate levels were increased in CSF a nd blood. Urinary organic acid profile was compatible with PDH deficie ncy. PDH activity was normal in fibroblasts, lymphocytes, and muscle. The PDH E1-alpha gene was sequenced and a single base mutation was fou nd within the regulatory phosphorylation site in exon 10. It is postul ated that this mutation causes a cerebral form of PDH deficiency. Tiss ue-specific expression of the disease could be explained by differenti al X chromosome inactivation because the PDH E1-alpha gene is located on this chromosome. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.