title: Long survival in Leigh syndrome: new cases and review of literature.
abstract: Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder with characteristic bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is commonly associated with systemic cytochrome c oxidase (COX) deficiency and mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or maintenance factor of COX. The clinical course is dominated by neurodevelopmental regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea) with death often occurring before the age of 10 years. Herein, we present three sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT) that is predicted to result in a truncated protein with loss of function. Our patients show heterogeneous clinical findings with different distribution patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well as a Chiari malformation with hydrocephalus in one patient. However, all three siblings show an unusual long survival (12 years and>16 years). COX activity was not detectable in one patient and strongly reduced in the other two. We discuss these findings with respect to a review of the literature. A total of 15 additional patients with survival>14 years have been reported so far. Overall, no clear genotype-phenotype correlations are detectable among these patients.
authors.affiliation: Department of Neuropediatrics, University Children's Hospital, Ruhr University, Bochum, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Aulbert
authors.affiliation: Department of Neuropediatrics, University Children's Hospital, Ruhr University, Bochum, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weigt-Usinger
authors.affiliation: Department of Neuropediatrics, University Children's Hospital, Ruhr University, Bochum, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Thiels
authors.affiliation: Department of Neuropediatrics, University Children's Hospital, Ruhr University, Bochum, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Köhler
authors.affiliation: Department of Neurology, University Hospital Bergmannsheil, Ruhr University, Bochum, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.affiliation: Department of Neurology, University Hospital Bergmannsheil, Ruhr University, Bochum, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schreiner
authors.affiliation: Department of Human Genetics, Ruhr University, Bochum, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
authors.affiliation: Department of Pediatric Pneumology and Immunology, University Children's Hospital, Ruhr University, Bochum, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Rothoeft
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders (NCMD) at the Department of Pediatrics and the Institute for Genetic and Metabolic Disease (IGMD), Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Saskia Brigitte
authors.initials: SB
authors.lastname: Wortmann
authors.affiliation: Institute of Diagnostic Radiology, Interventional Radiology and Nuclear Medicine, University Hospital Bergmannsheil, Ruhr University, Bochum, Germany.
authors.forename: Christoph Malte
authors.initials: CM
authors.lastname: Heyer
authors.affiliation: Laboratory for Molecular Genetics and Metabolic Diseases, Munich, Germany.
authors.forename: Teodor
authors.initials: T
authors.lastname: Podskarbi
authors.affiliation: Department of Neuropediatrics, University Children's Hospital, Ruhr University, Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lücke
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics* / Q000401:mortality* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D035781:Siblings
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092928:Surf-1 protein