Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review
BackgroundPrimary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as s...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2024.1378083/full |
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| author | Lei Zhang Gentzon Hall Peitong Han Chunzhen Li Jieyuan Cui |
| author_facet | Lei Zhang Gentzon Hall Peitong Han Chunzhen Li Jieyuan Cui |
| author_sort | Lei Zhang |
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| description | BackgroundPrimary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS).MethodsFour SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing.ResultsClinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease.ConclusionsCOQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis. |
| format | Article |
| id | doaj-art-194a2764d7e848769cecd44e3ed892fa |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Pediatrics |
| spelling | doaj-art-194a2764d7e848769cecd44e3ed892fa2025-01-14T06:10:44ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-01-011210.3389/fped.2024.13780831378083Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature reviewLei Zhang0Gentzon Hall1Peitong Han2Chunzhen Li3Jieyuan Cui4Department of Pediatric Nephrology, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, ChinaDuke University School of Medicine, Duke Molecular Physiology Institute, Durham, NC, United StatesDepartment of Pediatric Nephrology, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, ChinaDepartment of Pediatric Nephrology, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, ChinaDepartment of Pediatric Nephrology, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, ChinaBackgroundPrimary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS).MethodsFour SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing.ResultsClinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease.ConclusionsCOQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.https://www.frontiersin.org/articles/10.3389/fped.2024.1378083/fullCOQ8B variantglomerulopathysteroid-resistant nephrotic syndromefocal segmental glomerulosclerosisautosomal recessive |
| spellingShingle | Lei Zhang Gentzon Hall Peitong Han Chunzhen Li Jieyuan Cui Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review Frontiers in Pediatrics COQ8B variant glomerulopathy steroid-resistant nephrotic syndrome focal segmental glomerulosclerosis autosomal recessive |
| title | Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review |
| title_full | Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review |
| title_fullStr | Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review |
| title_full_unstemmed | Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review |
| title_short | Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review |
| title_sort | clinical follow up of 2 families with glomerulopathy caused by coq8b gene variants and literature review |
| topic | COQ8B variant glomerulopathy steroid-resistant nephrotic syndrome focal segmental glomerulosclerosis autosomal recessive |
| url | https://www.frontiersin.org/articles/10.3389/fped.2024.1378083/full |
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