Severe Neurological Presentation in Siblings With COQ5-Related Primary Coenzyme Q10 Deficiency: Expanding Clinical and Molecular Spectrum
Issued Date
2025-11-01
Resource Type
ISSN
21928304
eISSN
21928312
Scopus ID
2-s2.0-105021256907
Journal Title
Jimd Reports
Volume
66
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Jimd Reports Vol.66 No.6 (2025)
Suggested Citation
Wongkittichote P., Guerra R.M., Wegner D.J., Toy S., Hauer J.A., Pagliarini D.J., Granadillo J.L. Severe Neurological Presentation in Siblings With COQ5-Related Primary Coenzyme Q10 Deficiency: Expanding Clinical and Molecular Spectrum. Jimd Reports Vol.66 No.6 (2025). doi:10.1002/jmd2.70038 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113106
Title
Severe Neurological Presentation in Siblings With COQ5-Related Primary Coenzyme Q10 Deficiency: Expanding Clinical and Molecular Spectrum
Corresponding Author(s)
Other Contributor(s)
Abstract
Coenzyme Q<inf>10</inf> (CoQ<inf>10</inf>) is a coenzyme and antioxidant involved in multiple bioenergetic and biosynthetic processes, particularly within mitochondria. The biosynthesis of CoQ<inf>10</inf> is a tightly regulated process that involves multiple enzymes, including the methyltransferase COQ5. Genetic defects in COQ5 have recently been associated with autosomal recessive COQ5-related primary CoQ<inf>10</inf> deficiency. The clinical manifestations of seven individuals previously reported were primarily neurological and ophthalmological. Here, we report two siblings with profound developmental delay and brain imaging consistent with multistage strokes. Clinical exome sequencing revealed compound heterozygous variants in COQ5, including one frameshift deletion and one missense variant. Our functional complementation studies demonstrate that a Saccharomyces cerevisiae COQ5 ortholog harboring the corresponding missense variant fails to fully rescue coq5∆ CoQ<inf>6</inf> production, leading to the accumulation of CoQ biosynthetic intermediates. After the diagnosis, CoQ<inf>10</inf> supplementation was started on the proband, leading to subjective clinical improvement. We describe new cases of COQ5-related primary CoQ<inf>10</inf> deficiency and expand the phenotypic and molecular spectrum of the disease. We also establish a yeast system to evaluate the effects of the variants in COQ5 and support the use of CoQ<inf>10</inf> supplementation for patients with COQ5-related primary CoQ<inf>10</inf> deficiency.