Objective:
The purpose of this study was to find the molecular cause of a familial disease with findings consistent with COQ10 deficiency and describe the clinical, biochemical and molecular characteristics of the disease.
Background:
Coenzyme Q (ubiquinone) is a lipophilic redox molecule, essential for diverse cellular roles. Diseases of CoQ 10 deficiency have heterogeneous clinical presentations; encephalopathy, Ataxia , seizures, cognitive
impairment, etc.
While several genes in the CoQ 10 biosynthesis pathway have been implicated in primary CoQ 10 deficiency , no human phenotype attributable to COQ5 mutations has been described.
We report for the first time patients with encephalomyopathy, cerebellar ataxia and additional findings in a multiplex non-consanguineous family with CoQ10 deficiency due to a biallelic duplication in COQ5.
Methods:
We studied a family of non -consanguines Iraqi-Jewish descent, of which three female siblings had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, and cognitive disability. Molecular and biochemical investigations were performed.
Results:
Whole-genome sequencing identified a biallelic duplications in the COQ5 gene, leading to reduced levels of CoQ10 in peripheral white blood cells and muscle tissue from affected members.
CoQ10 supplementation led to clinical improvement and increased the concentrations of CoQ10 in blood.
Discussion:
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.
Early diagnosis of this disease may be of great value for for successful treatment and intervention strategies.
