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Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3.
Clin Genet. 2016 Aug; 90(2):156-60.CG

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+Show Affiliations

Department of Neurology, Columbia University Medical Center, New York, NY, USA. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy. Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.Department of Neurology, Columbia University Medical Center, New York, NY, USA.Department of Neurology, Columbia University Medical Center, New York, NY, USA.Department of Neurology, Columbia University Medical Center, New York, NY, USA.Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

26818466

Citation

Barca, E, et al. "Cerebellar Ataxia and Severe Muscle CoQ10 Deficiency in a Patient With a Novel Mutation in ADCK3." Clinical Genetics, vol. 90, no. 2, 2016, pp. 156-60.
Barca E, Musumeci O, Montagnese F, et al. Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. Clin Genet. 2016;90(2):156-60.
Barca, E., Musumeci, O., Montagnese, F., Marino, S., Granata, F., Nunnari, D., Peverelli, L., DiMauro, S., Quinzii, C. M., & Toscano, A. (2016). Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. Clinical Genetics, 90(2), 156-60. https://doi.org/10.1111/cge.12742
Barca E, et al. Cerebellar Ataxia and Severe Muscle CoQ10 Deficiency in a Patient With a Novel Mutation in ADCK3. Clin Genet. 2016;90(2):156-60. PubMed PMID: 26818466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. AU - Barca,E, AU - Musumeci,O, AU - Montagnese,F, AU - Marino,S, AU - Granata,F, AU - Nunnari,D, AU - Peverelli,L, AU - DiMauro,S, AU - Quinzii,C M, AU - Toscano,A, Y1 - 2016/02/16/ PY - 2015/12/23/received PY - 2016/01/20/revised PY - 2016/01/21/accepted PY - 2016/1/29/entrez PY - 2016/1/29/pubmed PY - 2017/5/23/medline KW - ADCK3 KW - CoQ10 KW - cerebellar ataxia KW - mitochondrial disorders KW - neurodegenerative diseases SP - 156 EP - 60 JF - Clinical genetics JO - Clin Genet VL - 90 IS - 2 N2 - 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. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/26818466/Cerebellar_ataxia_and_severe_muscle_CoQ10_deficiency_in_a_patient_with_a_novel_mutation_in_ADCK3_ L2 - https://doi.org/10.1111/cge.12742 DB - PRIME DP - Unbound Medicine ER -