Clinical Spectrum and Genotype-Phenotype Associations in Coenzyme Q10 Deficiency Nephropathy in a Chinese Cohort

Background: Primary Coenzyme Q10 (CoQ10) deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome, mainly associated with disease-causing variants in the genes COQ2, COQ6, COQ8B, PDSS1 and PDSS2. Data from Chinese Children Genetic Kidney Disease Database (CCGKDD) revealed that CoQ10 deficiency nephropathy is a major type of hereditary glomerular disease in China, accounting for 12% of end stage of kidney disease. It is emergent to enhance our understanding of the clinical spectrum and genetic underpinnings of CoQ10 deficiency nephropathy in Chinese cohort. Methods: A systematic literature review, CCGKDD registries queries and an online survey were performed to collecting comprehensive clinical and genetic data of CoQ10 deficiency nephropathy cases. Results: We included 188 cases in the current study. Isolated kidney involvement at diagnosis occurred in 7.9% (15/188) of COQ2, 3.7% (7/188) of COQ6, 86.2% (162/188) of COQ8B, 1.1% (2/188) of PDSS1 and 1.1% (2/188) of PDSS2 variant individuals. Kidney disease was first diagnosed at median age 1.8, 2.3, 7.8, 1.0 and 6.5 years old in individuals with disease-causing variants in COQ2, COQ6, COQ8B, PDSS1 and PDSS2 respectively. 46% of patients with COQ2 and COQ6 variants progressed to kidney failure by age 5 years old, 45.7% of patients with COQ8B variants progressed to kidney failure by age 9 years old. For clinical features, vesicoureteral reflux, renal agenesis and kidney cyst, and congenital absence of thumb and scaphoid bone could be observed in COQ8B deficiency cases. Hiatal hernia might be a new phenotype of patients with COQ2 deficiency. Early detection of COQ8B nephropathy following CoQ10 supplementation slowed the progression of kidney dysfunction of 27% of patients. 64.7% of patients in the study had received kidney transplant, none of the cases experienced loss of function of transplanted kidney with CoQ10 supplementation. Conclusion: Our study enhances the understanding of clinical spectrum and genetic underpinnings of CoQ10 deficiency nephropathy in the Chinese cohort. Early supplementation with exogenous CoQ10 can slow the progression of kidney impairment, however, it shows limited efficacy in 63% of cases with CoQ10 deficiency nephropathy, indicating a lack of targeted intervention strategies, which need to be further study. Funding: Government Support – Non-U.S.