NEUROPATHOLOGICAL FINDINGS OF A PATIENT WITH PYRUVATE DEHYDROGENASE-E1-ALPHA DEFICIENCY PRESENTING AS A CEREBRAL LACTIC-ACIDOSIS

Neuropathological findings are reported of a 6-month-old female child with a ''cerebral'' lactic acidosis. A mutation in the pyruvate dehydr ogenase (PDH) E1alpha gene was found. Gross examination of the brain r evealed a severe thinning of the cerebral parenchyma marked hydrocepha lus sparing the aqueduct and fourth ventricle, agenesis of the corpus callosum and heterotopic noduli of gray matter in subependymal regions . Microscopical examination showed heterotopic inferior olives, absent pyramids and focal neuroglial overgrowth into meninges. In addition s ome heterotopia of Purkinje cells and dysplasia of the dentate nuclei were observed. There was a marked vascular proliferation with many thi n-walled, congestive vessels in the cerebral and cerebellar white matt er. and to a lesser extent in the striatum. To our knowledge these cer ebellar and vascular abnormalities have not been reported before in pa tients with ''cerebral'' lactic acidosis.The combination of these neur opathological findings might be characteristic for PDH deficiency and more specifically for its E1alpha subtype. Neuropathological examinati on could lead to the retrospective diagnosis of PDH E1alpha deficiency in those cases where biochemical investigations were not or incomplet ely performed. This may have potential implications for genetic counse ling.