Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3.
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Barca E, Musumeci O, Montagnese F, Marino S, Granata F, Nunnari D, Peverelli L, DiMauro S, Quinzii CM, Toscano A
Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3.
Clin Genet. 2016 Aug;90(2):156-60. doi: 10.1111/cge.12742. Epub 2016 Feb 16.
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- 26818466 [ View in PubMed]
- 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.