Case Report: Pediatric nephrology—expanding the genotypic spectrum of COQ2-related nephropathy with a novel splice site variant in CoQ10-responsive SRNS

Coenzyme Q10, also known as CoQ10, CoQ, and ubiquinone is an essential component of the mitochondrial electron-transport chain and functions as an energy transfer molecule as well as a redox carrier and is a lipid-soluble antioxidant. Biallelic pathogenic variants in one of the 10 genes encoding proteins involved in its synthesis, establishes the diagnosis of primary CoQ10 deficiency. COQ2 , or parahydroxybenzoate-polyprenyltransferase (EC 2.5.1.39), catalyzes one of the final reactions in the biosynthesis of CoQ, the prenylation of parahydroxybenzoate with an all-trans polyprenyl group. COQ2 related CoQ10 deficiency can present with multiple system atrophy, cardiomyopathy and steroid resistant nephrotic syndrome (SRNS). Multiple papers have suggested CoQ supplement can treat SRNS. We report a 9-year-old girl presenting with steroid-resistant nephrotic syndrome, whose renal biopsy revealed focal segmental glomerulosclerosis. She showed only a partial response to combined therapy with tacrolimus, lisinopril, and losartan. Whole exome sequencing identified two compound heterozygous variants in the COQ2 gene (NM_015697.7): a known pathogenic variant, c.683A>G, inherited from her father, and a novel splice-site variant, c.692+3A>G, inherited from her mother and currently classified as a variant of uncertain significance (VUS). Notably, previously reported patients carrying the c.683A>G variant typically present with early-onset, severe disease. In contrast, our patient’s relatively late onset and isolated nephropathy suggests that the novel variant may be pathogenic but associated with a milder phenotype. Prompt genetic diagnosis enabled early initiation of high-dose CoQ10 supplementation (ubiquinone, 30 mg/kg/day), which led to marked clinical improvement and may have prevented further renal function deterioration or the development of other systemic manifestations.