title: Infantile leukoencephalopathy owing to mitochondrial enzyme dysfunction.
abstract: Mitochondrial disease is classically associated with deep gray-matter lesions. When white matter is involved, the lesions are typically subcortical and overshadowed by more significant disease in the gray matter. We report six infants in five families who developed neurodegenerative diseases characterized primarily by abnormalities in deep white-matter structures such as the periventricular region, internal capsule, and corpus callosum. Five patients had impairments of mitochondrial enzymes, including a pre-electron transport chain defect and defects in respiratory chain complexes I, III, and IV (cytochrome-c oxidase). One patient, the sibling of one of the others, was diagnosed clinically with complex III deficiency. These six patients, along with others in the literature, appear to represent a distinct syndrome of mitochondrial infantile leukoencephalopathy. Our observations suggest that infants with leukoencephalopathies, especially leukodystrophies, who do not have one of the more common causes of white-matter disease should be evaluated for mitochondrial dysfunction.
authors.affiliation: Division of Neurology, Children's Hospital of Philadelphia, PA, USA. peter.kang@tch.harvard.edu
authors.forename: Peter B
authors.initials: PB
authors.lastname: Kang
authors.forename: Jill V
authors.initials: JV
authors.lastname: Hunter
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Melvin
authors.forename: Mary A
authors.initials: MA
authors.lastname: Selak
authors.forename: Eric N
authors.initials: EN
authors.lastname: Faerber
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kaye
mesh_terms: D003337:Corpus Callosum / Q000473:pathology; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020772:Internal Capsule / Q000473:pathology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III