COQ2 nephropathy: a treatable cause of nephrotic syndrome in children.

Background: Nephrotic syndrome can be caused by a subgroup of mitochondrial diseases classified as primary coenzyme Q (CoQ) deficiency. Pathogenic COQ2 variants are a cause of primary CoQ deficiency and present with phenotypes ranging from isolated nephrotic syndrome to fatal multisystem disease.

Case-diagnosis/treatment: We report three pediatric patients with COQ2 variants presenting with nephrotic syndrome. Two of these patients had normal leukocyte CoQ levels prior to treatment. Pathologic findings varied from mesangial sclerosis to focal segmental glomerulosclerosis, with all patients having abnormal appearing mitochondria on kidney biopsy. In two of the three patients treated with CoQ supplementation, the nephrotic syndrome resolved; and at follow-up, both have normal renal function and stable proteinuria.

Conclusions: COQ2 nephropathy should be suspected in patients presenting with nephrotic syndrome, although less common than disease due to mutations in NPHS1, NPHS2, and WT1. The index of suspicion should remain high, and we suggest that providers consider genetic evaluation even in patients with normal leukocyte CoQ levels, as levels may be within normal range even with significant clinical disease. Early molecular diagnosis and specific treatment are essential in the management of this severe yet treatable condition.