Abstract:

This study retrospectively analyzed clinical data from a family with childhood isolated nephrotic syndrome (INS) caused by compound heterozygous mutations in the COQ2 gene, to explore the correlations between genotype, clinical phenotypic characteristics, and prognosis. Two siblings in the family presented with INS, and renal pathological examination revealed focal segmental glomerulosclerosis (FSGS). Genetic testing identified that both siblings carried compound heterozygous mutations in COQ2: c.233T>G (NM_001358921.2), p.(Met78Arg) and c.823A>G (NM_001358921.2), p.(Thr275Ala), with c.233T>G being a de novo variant. The proband (elder brother) initially underwent genetic testing that failed to identify the etiology; treatment with glucocorticoids and immunosuppressants was ineffective, leading to progressive disease deterioration and eventual death. His younger sister, however, received an early diagnosis via reanalysis of the proband’s original sequencing data shortly after symptom onset. She was promptly administered high-dose coenzyme Q₁₀ replacement therapy and had glucocorticoids gradually tapered and discontinued. After one year of treatment, her urinary protein levels decreased significantly, and clinical symptoms and laboratory indicators improved markedly, with a favorable prognosis. This study confirms the critical value of genetic testing and periodic reanalysis of sequencing data in the diagnosis and management of such inherited kidney diseases, as well as the efficacy of early clinical intervention in improving patient outcomes. It provides important references for the diagnosis, treatment, and genetic counseling of primary coenzyme Q₁₀ deficiency-related nephropathy.

Key words: COQ2 gene, primary coenzyme Q₁₀ deficiency, isolated nephrotic syndrome, child