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Berardo et al. J Transl Genet Genom 2020;4:22-35 Journal of Translational
DOI: 10.20517/jtgg.2020.02 Genetics and Genomics

Review Open Access

Redefining infantile-onset multisystem phenotypes
of coenzyme Q -deficiency in the next-generation
10
sequencing era

Andres Berardo, Catarina M. Quinzii

Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.

Correspondence to: Associate Prof. Catarina M. Quinzii, Department of Neurology, Columbia University Medical Center, 630
W 168th street, P&S 4-424A, New York, NY 10032, USA. E-mail: cmq2101@cumc.columbia.edu
How to cite this article: Berardo A, Quinzii CM. Redefining infantile-onset multisystem phenotypes of coenzyme Q -deficiency
10
in the next-generation sequencing era. J Transl Genet Genom 2020;4:22-35. https://doi.org/10.20517/jtgg.2020.02
Received: 21 Jan 2020 First Decision: 26 Feb 2020 Revised: 23 Mar 2020 Accepted: 8 Apr 2020 Available online: 23 Apr 2020

Science Editor: Andrea L. Gropman Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Primary coenzyme Q 10 (CoQ 10 ) deficiency encompasses a subset of mitochondrial diseases caused by mutations
affecting proteins involved in the CoQ 10 biosynthetic pathway. One of the most frequent clinical syndromes
associated with primary CoQ 10 deficiency is the severe infantile multisystemic form, which, until recently, was
underdiagnosed. In the last few years, the availability of genetic screening through whole exome sequencing
and whole genome sequencing has enabled molecular diagnosis in a growing number of patients with this
syndrome and has revealed new disease phenotypes and molecular defects in CoQ 10 biosynthetic pathway genes.
Early genetic screening can rapidly and non-invasively diagnose primary CoQ 10 deficiencies. Early diagnosis is
particularly important in cases of CoQ 10 deficient steroid-resistant nephrotic syndrome, which frequently improves
with treatment. In contrast, the infantile multisystemic forms of CoQ 10 deficiency, particularly when manifesting
with encephalopathy, present therapeutic challenges, due to poor responses to CoQ 10 supplementation.
Administration of CoQ 10 biosynthetic intermediate compounds is a promising alternative to CoQ 10 ; however,
further pre-clinical studies are needed to establish their safety and efficacy, as well as to elucidate the mechanism
of actions of the intermediates. Here, we review the molecular defects causes of the multisystemic infantile
phenotype of primary CoQ 10 deficiency, genotype-phenotype correlations, and recent therapeutic advances.

Keywords: Coenzyme Q 10 , coenzyme Q 10 deficiency, coenzyme Q biosynthesis, nephrotic syndrome, cardiopathy,
encephalopathy

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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