Primary coenzyme Q10 deficiency due to COQ8A gene mutations

• Published in: Molecular genetics & genomic medicine Vol. 8; no. 10; pp. e1420 - n/a
• Main Authors: Zhang, Linwei, Ashizawa, Tetsuo, Peng, Dantao
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.10.2020; John Wiley and Sons Inc; Wiley
• Subjects: Age; Amino acids; Ataxia; Atrophy; Cerebellar ataxia; Cerebellum; Coenzyme Q10; Constipation; COQ8A gene; deficiency; Deoxyribonucleic acid; DNA; Dysautonomia; Electron transport; Erectile dysfunction; Families & family life; Friedreich's ataxia; Gait; Intellectual disabilities; Intelligence tests; Intolerance; Kidney diseases; Kinases; Lactic acid; Magnetic resonance imaging; Mitochondria; Movement disorders; Mutation; mutations; Original; Patients; Plasma; Scoliosis; Signs and symptoms; Spine; Spine (lumbar); Steroids; Tremor; Tremor (Muscular contraction); Urinary incontinence; China; Japan; coenzyme Q10; mutations; deficiency; COQ8A gene
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1420

Background Primary deficiency of coenzyme Q10 deficiency‐4 (COQ10D4) is an autosomal recessive cerebellar ataxia with mitochondrial respiratory chain disfunction. The main clinical manifestation involves early‐onset exercise intolerance, progressive cerebellar ataxia, and movement disorders. COQ8A gene mutations are responsible for this disease. Here, we provide clinical, laboratory, and genetic findings of a patient with cerebellar ataxia caused by compound heterozygous mutations in COQ8A gene. Methods A male patient from a non‐consanguineous Chinese family underwent detailed physical and auxiliary examination. After exclusion of acquired causes of ataxia, Friedreich's Ataxia, and common types of spinocerebellar ataxia, the patient was subjected to whole exome sequencing (WES) followed by confirmation of sequence variants using Sanger sequencing. His asymptomatic parents, two brothers and one sister were genotyped for these variants. Results This patient showed early‐onset exercise intolerance and progressive cerebellar ataxia, wide‐based gait and tremor, accompanied by symptoms of dysautonomia. His serum lactate level was elevated and plasma total Coenzyme Q10 (CoQ10) was decreased. Brain MRI showed cerebellar atrophy, and X‐ray of the spine revealed thoraco‐lumbar scoliosis. Compound heterozygous mutations in the COQ8A gene were identified through WES: c.1844_1845insG, p.Ser616Leufs*114 and c.902G>A, p.Arg301Gln. After treatment with ubidecarenone, 40 mg three times per day for 2 years, the symptoms dramatically improved. Conclusions We identified a patient with COQ10D4 caused by novel COQ8A mutations. Our findings widen the spectrum of COQ8A gene mutations and clinical manifestations. We identified a patient with COQ10D4 caused by novel COQ8A mutations through WES. Our findings widen the spectrum of COQ8A gene mutations and clinical manifestations.