Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3

E. Barca, O. Musumeci, F. Montagnese, S. Marino, F. Granata, D. Nunnari, L. Peverelli, S. DiMauro, C. M. Quinzii, A. Toscano

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)156-160
Number of pages5
JournalClinical Genetics
Volume90
Issue number2
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • ADCK3
  • cerebellar ataxia
  • CoQ10
  • mitochondrial disorders
  • neurodegenerative diseases

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    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), 156-160. https://doi.org/10.1111/cge.12742