Kidney Week

Abstract: PO1659

Features of Hereditary Nephropathy with COQ8B Mutation

Session Information

• Genetic Diseases of the Kidneys: Non-Cystic - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Author

• Lee, Jiwon M., Chungnam National University, Daejeon, Daejeon, Korea (the Republic of)

Jiwon M. Lee,

Background

Mutations in the genes related to biosynthesis of Coenzyme Q 10 (CoQ₁₀, ubiquinone) cause primary CoQ₁₀ deficiency resulting in various clinical phenotypes. COQ8B (also known as ADCK4) has been first reported in association with nephropathy in 2013, and previously a Korean cohort has reported six patients, notably accompanied by medullary nephrocalcinosis in all the six cases. Because these patients can benefit from CoQ₁₀ replacement, early differential diagnosis is essential. This study systematically reviewed clinical features and genotypes of patients with COQ8B-associated nephropathy.

Methods

Electronic databases were searched using related terms (till March 30, 2020). This report adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

Results

From 126 articles searched, there were 11 eligible studies with 49 patients with COQ8B-associated nephropathy. Of them, 26 patients were Caucasian and 21 were Asian (the rest had no data regarding ethnicity). Female to male ratio was 2:1. Median age at diagnosis was 14.6 years. Proteinuria was reported in 100% of the patients with median serum albumin level of 3.7 g/dL and creatinine level of 1.45 mg/dL. Twenty two patients (43%) had chronic kidney disease and twelve patients had end-stage renal disease (25%)/ Transplantation was performed in 6 cases out of which 5 had no recurrence. Of 33 patients available for pathology reports, most (32/33, 97%) patients showed histology compatible with focal segmental glomerulosclerosis (FSGS) and seven (14%) patients had abnormal mitochondrial aggregation in the podocyte cytoplasm visualized by electon microscopy. Seven (14%) patients presented with medullary nephrocalcinosis who were notably all Koreans. Outcomes related to CoQ₁₀ replacement was reported in 14 cases and half of them reported partial or complement remission. Effect of calcineurin inhibitors were reported in 7 cases which showed partial remission in 4 cases.

Conclusion

COQ8B-associated FSGS is a rare hereditary nephropathy which can greatly benefit from early diagnosis and CoQ₁₀ supplement. Aberrant mitochondrial accumulation in the cytoplasm of the podocytes and increased medullary echogenicity may add to diagnostic suspicion. So far, all patients with COQ8B mutation reported in South Korea had medullary nephrocalcinosis.