title: Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3.
abstract: Inherited ataxias are a group of heterogeneous disorders in children or adults but their genetic definition remains still undetermined in almost half of the patients. However, CoQ10 deficiency is a rare cause of cerebellar ataxia and ADCK3 is the most frequent gene associated with this defect. We herein report a 48 year old man, who presented with dysarthria and walking difficulties. Brain magnetic resonance imaging showed a marked cerebellar atrophy. Serum lactate was elevated. Tissues obtained by muscle and skin biopsies were studied for biochemical and genetic characterization. Skeletal muscle biochemistry revealed decreased activities of complexes I+III and II+III and a severe reduction of CoQ10 , while skin fibroblasts showed normal CoQ10 levels. A mild loss of maximal respiration capacity was also found by high-resolution respirometry. Molecular studies identified a novel homozygous deletion (c.504del_CT) in ADCK3, causing a premature stop codon. Western blot analysis revealed marked reduction of ADCK3 protein levels. Treatment with CoQ10 was started and, after 1 year follow-up, patient neurological condition slightly improved. This report suggests the importance of investigating mitochondrial function and, in particular, muscle CoQ10 levels, in patients with adult-onset cerebellar ataxia. Moreover, clinical stabilization by CoQ10 supplementation emphasizes the importance of an early diagnosis.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.|Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Barca
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.|IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Musumeci
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Montagnese
authors.affiliation: IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.|Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Marino
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Granata
authors.affiliation: IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Nunnari
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Peverelli
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Quinzii
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.|IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Toscano
mesh_terms: D001259:Ataxia / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002524:Cerebellar Ataxia / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D018389:Codon, Nonsense; D057210:Delayed Diagnosis; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics*; D018908:Muscle Weakness / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D012867:Skin / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000235:genetics
chemical_list: C553453:COQ8A protein, human; D018389:Codon, Nonsense; D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins; D014451:Ubiquinone; D019344:Lactic Acid; C024989:coenzyme Q10
keywords: ADCK3; CoQ10; cerebellar ataxia; mitochondrial disorders; neurodegenerative diseases
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