Mitochondrial Dysfunction due to Novel COQ8A Variation with Poor Response to CoQ10 Treatment: A Comprehensive Study and Review of Literatures.

Publisher: Springer Country of Publication: United States NLM ID: 101089443 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-4230 (Electronic) Linking ISSN: 14734222 NLM ISO Abbreviation: Cerebellum Subsets: MEDLINE

Publication: <2006->: New York : Springer
Original Publication: London : Martin Dunitz, c2002-

Ubiquinone*/analogs & derivatives ; Ubiquinone*/therapeutic use ; Ubiquinone*/deficiency ; Ubiquinone*/genetics ; Mitochondrial Diseases*/drug therapy ; Mitochondrial Diseases*/genetics; Humans ; Adolescent ; Mitochondrial Proteins/genetics ; Male ; Ataxia/drug therapy ; Ataxia/genetics ; Mitochondria/drug effects ; Mitochondria/metabolism ; Muscle Weakness/genetics ; Muscle Weakness/drug therapy

COQ8A plays an important role in the biosynthesis of coenzyme Q10 (CoQ10), and variations in COQ8A gene are associated with primary CoQ10 deficiency-4 (COQ10D4), also known as COQ8A-ataxia. The current understanding of the association between the specific variant type, the severity of CoQ10 deficiency, and the degree of oxidative stress in individuals with primary CoQ10 deficiencies remains uncertain. Here we provide a comprehensive analysis of the clinical and genetic characteristics of an 18-year-old patient with COQ8A-ataxia, who exhibited novel compound heterozygous variants (c.1904_1906del and c.637C > T) in the COQ8A gene. These variants reduced the expression levels of COQ8A and mitochondrial proteins in the patient's muscle and skin fibroblast samples, contributed to mitochondrial respiration deficiency, increased ROS production and altered mitochondrial membrane potential. It is worth noting that the optimal treatment for COQ8A-ataxia remains uncertain. Presently, therapy consists of CoQ10 supplementation, however, it did not yield significant improvement in our patient's symptoms. Additionally, we reviewed the response of CoQ10 supplementation and evolution of patients in previous literatures in detail. We found that only half of patients could got notable improvement in ataxia. This research aims to expand the genotype-phenotype spectrum of COQ10D4, address discrepancies in previous reviews regarding the effectiveness of CoQ10 in these disorders, and help to establish a standardized treatment protocol for COQ8A-ataxia.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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No.82301590 the National Natural Science Foundation of China; No.82071412 the National Natural Science Foundation of China; No.82171394 the National Natural Science Foundation of China; 2023M742116 China Postdoctoral Science Foundation; ZR2023QH106 Natural Science Foundation of Shandong Province; SDBX2022061 Shandong Provincial Postdoctoral Innovation Talent Support Program; No.2021YFC2700904 Grants from the National Key R&D Program of China; 20-3-4-42-nsh People's Benefit Project of Science and Technology in Qingdao

Keywords: COQ8A gene; Cerebellar ataxia; CoQ10; Mitochondrial; Primary CoQ10 deficiency

1339-63-5 (Ubiquinone)
EJ27X76M46 (coenzyme Q10)
0 (COQ8A protein, human)
0 (Mitochondrial Proteins)

Coenzyme Q10 Deficiency

Date Created: 20240301 Date Completed: 20241018 Latest Revision: 20241022

20241022

10.1007/s12311-024-01671-4

38429489