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A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency

Lookup NU author(s): Dr Langping He, Professor Robert Taylor


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© 2017 Wiley Periodicals, Inc. Primary coenzyme Q10 (CoQ10; MIM# 607426) deficiencies are an emerging group of inherited mitochondrial disorders with heterogonous clinical phenotypes. Over a dozen genes are involved in the biosynthesis of CoQ10, and mutations in several of these are associated with human disease. However, mutations in COQ5 (MIM# 616359), catalyzing the only C-methylation in the CoQ10 synthetic pathway, have not been implicated in human disease. Here, we report three female siblings of Iraqi-Jewish descent, who had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, and cognitive disability. Whole-exome and subsequent whole-genome sequencing identified biallelic duplications in the COQ5 gene, leading to reduced levels of CoQ10 in peripheral white blood cells of all affected individuals and reduced CoQ10 levels in the only muscle tissue available from one affected proband. CoQ10 supplementation led to clinical improvement and increased the concentrations of CoQ10 in blood. This is the first report of primary CoQ10 deficiency caused by loss of function of COQ5, with delineation of the clinical, laboratory, histological, and molecular features, and insights regarding targeted treatment with CoQ10 supplementation.

Publication metadata

Author(s): Malicdan MCV, Vilboux T, Ben-Zeev B, Guo J, Eliyahu A, Pode-Shakked B, Dori A, Kakani S, Chandrasekharappa SC, Ferreira CR, Shelestovich N, Marek-Yagel D, Pri-Chen H, Blatt I, Niederhuber JE, He L, Toro C, Taylor RW, Deeken J, Yardeni T, Wallace DC, Gahl WA, Anikster Y

Publication type: Article

Publication status: Published

Journal: Human Mutation

Year: 2018

Volume: 39

Issue: 1

Pages: 69-79

Print publication date: 01/01/2018

Online publication date: 16/10/2017

Acceptance date: 11/09/2017

ISSN (print): 1059-7794

ISSN (electronic): 1098-1004

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/humu.23345


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