title: Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption.
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. 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.
authors.affiliation: Neonatal Intensive Care Unit, Isala Clinics, Zwolle, The Netherlands.
authors.forename: H L M
authors.initials: HL
authors.lastname: van Straaten
authors.forename: J P
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: J M F
authors.initials: JM
authors.lastname: Trijbels
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: D
authors.initials: D
authors.lastname: Troost
authors.forename: J M
authors.initials: JM
authors.lastname: Rozemuller
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: L S
authors.initials: LS
authors.lastname: de Vries
authors.forename: M
authors.initials: M
authors.lastname: Schuelke
authors.forename: P G
authors.initials: PG
authors.lastname: Barth
mesh_terms: D000140:Acidosis, Lactic / Q000151:congenital* / Q000473:pathology; D001921:Brain / Q000002:abnormalities*; D030401:Cytochrome-c Oxidase Deficiency / Q000473:pathology*; D042967:Electron Transport Complex I / Q000172:deficiency*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male
chemical_list: D042967:Electron Transport Complex I