Familial COQ8B-Associated Glomerulopathy: Divergent Long-Term Outcomes and Adult Detection Through Cascade Testing

COQ8B (formerly ADCK4)-associated glomerulopathy is an autosomal recessive primary coenzyme Q10 deficiency that typically presents with proteinuria, focal segmental glomerulosclerosis and progressive kidney dysfunction during childhood or adolescence. We report extended longitudinal follow-up of a family carrying the homozygous COQ8B c.1339dupG, p.(Glu447Glyfs*10) variant, demonstrating marked intrafamilial phenotypic heterogeneity despite an identical genotype. Two homozygous siblings developed kidney failure in childhood or adolescence and underwent living-related kidney transplantation, with prolonged allograft survival and no clinical recurrence of the native disease. In contrast, a third homozygous sibling was identified through cascade testing at age 24 with preserved kidney function and non-nephrotic proteinuria and has remained free of kidney failure for more than 10 years. The fourth sibling, who was heterozygous, remained clinically unaffected and both heterozygous parental donors maintained normal kidney function without proteinuria during long-term follow-up. This family illustrates the broad clinical spectrum of COQ8B-associated glomerulopathy and shows that identical homozygous variants may be associated with markedly divergent long-term kidney trajectories. Cascade testing may identify mildly affected adults before advanced kidney impairment and should be considered an integral component of familial evaluation in genetically defined glomerular disease.