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.