Abstract
Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a complex neuromigrational disorder including ependymal cysts, leptomeningeal and subcortical heterotopia, polymicrogyria, multifocal cerebral calcifications, agenesis of the corpus callosum, and spongiform changes in brainstem and cerebellum. Intractable lactic acidosis, causing death on the first day of life, was associated with severely reduced activities of complex I and complex IV. The neuropathological and biochemical findings are closely similar to those reported previously by Samsom et al. in 1994. The findings confirm a distinct genetic syndrome of disrupted brain development with TORCH-like calcifications, and a complex neuronal migration disorder associated with a multicomplex disorder of the respiratory chain.
Key words
Cerebral calcifications - respiratory chain defects - corpus callosum agenesis - neuronal heterotopia - leptomeningeal heterotopia - ependymal cysts - microcephaly - congenital infection
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Prof. M. D. Peter G. Barth
Department of Pediatric Neurology Emma Children's Hospital/AMC
P.O. Box 22700
1100 DD Amsterdam
The Netherlands
eMail: p.g.barth@amc.uva.nl