Neuropathological findings of a patient with pyruvate dehydrogenase E1α 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 dehydrogenase (PDH) E1α gene was found. Gross examination of the brain revealed a severe thinning of the cerebral parenchym, a marked hydrocephalus 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 some heterotopia of Purkinje cells and dysplasia of the dentate nuclei were observed. There was a marked vascular proliferation with many thin-walled, congestive vessels in the cerebral and cerebellar white matter, and to a lesser extent in the striatum. To our knowledge these cerebellar and vascular abnormalities have not been reported before in patients with “cerebral” lactic acidosis. The combination of these neuropathological findings might be characteristic for PDH deficiency and more specifically for its E1α subtype. Neuropathological examination could lead to the retrospective diagnosis of PDH E1α deficiency in those cases where biochemical investigations were not or incompletely performed. This may have potential implications for genetic counseling.