title: A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder.
abstract: SUCLA2 defects have been associated with mitochondrial DNA (mtDNA) depletion and the triad of hypotonia, dystonia/Leigh-like syndrome, and deafness. A 9-year-old Brazilian boy of consanguineous parents presented with psychomotor delay, deafness, myopathy, ataxia, and chorea. Despite the prominent movement disorder, brain magnetic resonance imaging (MRI) was normal while1H-magnetic resonance spectroscopy (MRS) showed lactate peaks in the cerebral cortex and lateral ventricles. Decreased biochemical activities of mitochondrial respiratory chain enzymes containing mtDNA-encoded subunits and mtDNA depletion were observed in muscle and fibroblasts. A novel homozygous mutation in SUCLA2, the first one in the ligase coenzyme A (CoA) domain of the protein, was identified. Escalating doses of CoQ10up to 2000 mg daily were associated with improvement of muscle weakness and stabilization of the disease course. The findings indicate the importance of screening for mitochondrial dysfunction in patients with complex movement disorders without brain MRI lesions and further investigation for potential secondary CoQ10deficiency in patients with SUCLA2 mutations.
authors.affiliation: 1 Department of Neurology, Columbia University Medical Center, New York, NY, USA.|2 Universities of Turin and Bologna, Turin, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Garone
authors.affiliation: 3 Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Gurgel-Giannetti
authors.affiliation: 4 Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.affiliation: 1 Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Sindu
authors.initials: S
authors.lastname: Krishna
authors.affiliation: 5 Department of Pathology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.affiliation: 1 Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.affiliation: 1 Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D001259:Ataxia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002648:Child; D003937:Diagnosis, Differential; D006720:Homozygote; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009069:Movement Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D013389:Succinate-CoA Ligases / Q000235:genetics*; D014451:Ubiquinone / Q000172:deficiency / Q000235:genetics
chemical_list: D014451:Ubiquinone; D013389:Succinate-CoA Ligases; C518788:SUCLA2 protein, human
keywords: SUCLA2; brain MRI; coenzyme Q10; movement disorders