Cerebellar ataxia and severe muscle CoQ sub(10) deficiency in a patient with a novel mutation in ADCK3

• Published in: Clinical genetics Vol. 90; no. 2; pp. 156 - 160
• Main Authors: Barca, E, Musumeci, O, Montagnese, F, Marino, S, Granata, F, Nunnari, D, Peverelli, L, DiMauro, S, Quinzii, C M, Toscano, A
• Format: Journal Article
• Language: English
• Published: 01.08.2016
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12742

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, CoQ sub(10) 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 CoQ sub(10), while skin fibroblasts showed normal CoQ sub(10) 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 CoQ sub(10) was started and, after 1year follow-up, patient neurological condition slightly improved. This report suggests the importance of investigating mitochondrial function and, in particular, muscle CoQ sub(10) levels, in patients with adult-onset cerebellar ataxia. Moreover, clinical stabilization by CoQ sub(10) supplementation emphasizes the importance of an early diagnosis.