title: Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect.
abstract: Mitochondrial NADH: ubiquinone oxidoreductase (complex I) deficiency accounts for most defects in mitochondrial oxidative phosphorylation. Pathogenic mutations have been described in all 7 mitochondrial and 12 of the 38 nuclear encoded subunits as well as in assembly factors by interfering with the building of the mature enzyme complex within the inner mitochondrial membrane. We now describe a male patient with a novel homozygous stop mutation in the NDUFAF2 gene. The boy presented with severe apnoea and nystagmus. MRI showed brainstem lesions without involvement of basal ganglia and thalamus, plasma lactate was normal or close to normal. He died after a fulminate course within 2 months after the first crisis. Neuropathology verified Leigh disease. We give a synopsis with other reported patients. Within the clinical spectrum of Leigh disease, patients with mutations in NDUFAF2 present with a distinct clinical pattern with predominantly brainstem involvement on MRI. The diagnosis should not be missed in spite of the normal lactate and lack of thalamus and basal ganglia changes on brain MRI.
authors.affiliation: Institute of Human Genetics, TU Munich and Helmholtz Zentrum Mü nchen,Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Herzer
authors.forename: J
authors.initials: J
authors.lastname: Koch
authors.forename: H
authors.initials: H
authors.lastname: Prokisch
authors.forename: R
authors.initials: R
authors.lastname: Rodenburg
authors.forename: C
authors.initials: C
authors.lastname: Rauscher
authors.forename: W
authors.initials: W
authors.lastname: Radauer
authors.forename: R
authors.initials: R
authors.lastname: Forstner
authors.forename: P
authors.initials: P
authors.lastname: Pilz
authors.forename: B
authors.initials: B
authors.lastname: Rolinski
authors.forename: P
authors.initials: P
authors.lastname: Freisinger
authors.forename: J A
authors.initials: JA
authors.lastname: Mayr
authors.forename: W
authors.initials: W
authors.lastname: Sperl
mesh_terms: D001933:Brain Stem / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D042967:Electron Transport Complex I / Q000172:deficiency*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D024101:Mitochondrial Proteins / Q000172:deficiency*; D018832:Molecular Chaperones; D018482:Muscle, Skeletal / Q000201:enzymology; D009154:Mutation / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C501824:NDUFAF2 protein, human; D042967:Electron Transport Complex I