Abstract
Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease. We report two girls with ataxia and mitochondrial respiratory chain deficiency who were shown to have primary CoQ10 deficiency. Muscle histochemistry displayed signs of mitochondrial dysfunction—ragged red fibers, mitochondrial paracrystalline inclusions, and lipid deposits while biochemical analyses revealed complex II+III respiratory chain deficiencies. MRI brain demonstrated cerebral and cerebellar atrophy. Targeted molecular analysis identified a homozygous c.1015G>A, p.(Ala339Thr) COQ8A variant in subject 1, while subject 2 was found to harbor a single heterozygous c.1029_1030delinsCA variant predicting a p.Gln343_Val344delinsHisMet amino acid substitution. Subsequent investigations identified a large‐scale COQ8A deletion in trans to the c.1029_1030delinsCA allele. A skin biopsy facilitated cDNA studies that confirmed exon skipping in the fibroblast derived COQ8A mRNA transcript. This report expands the molecular genetic spectrum associated with COQ8A‐related mitochondrial disease and highlights the importance of thorough investigation of candidate pathogenic variants to establish phase. Rapid diagnosis is of the utmost importance as patients may benefit from therapeutic CoQ10 supplementation.
Highlights
Primary coenzyme Q10 (CoQ10, ubiquinone) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease with a variable age of onset.[1]
While Coenzyme Q10 (CoQ10) deficiency can occur secondary to statin therapy[4] or alternative gene defects,[5] most cases are caused by biallelic pathogenic variants affecting one of the nine enzymes involved in its biosynthesis via the mevalonate pathway.[6,7]
Histochemical and molecular genetic findings relating to two young, female patients, both of whom presented with early onset cerebellar ataxia and were found to harbor recessive pathogenic variants in COQ8A
Summary
Primary coenzyme Q10 (CoQ10, ubiquinone) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease with a variable age of onset.[1]. Histochemical and molecular genetic findings relating to two young, female patients, both of whom presented with early onset cerebellar ataxia and were found to harbor recessive pathogenic variants in COQ8A
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