Case Report: Membranous Nephropathy Secondary to Cobalamin C Disease

Wang, Qiang; Wang, Qi; Gao, Yanxia; Tang, Chenquan; Gao, Zhaoli; Hu, Zhao

doi:10.3389/fmed.2021.807017

Cited by 5 publications

(6 citation statements)

References 19 publications

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“…However, although TMA was the only kidney histologic pattern in our series, thrombocytopenia and serum markers of hemolysis with increased LDH, indirect bilirubin, and reticulocyte count were not prominent, and the preschool age of onset was most common. In the five reported Chinese cases with genetically proven child-and adolescence-onset cblC-associated renal disease (Table 2), a similar phenomenon was observed (10)(11)(12)(13)(14). MMACHC genotypes may not explain the reasons for these differences.…”

Section: Discussionsupporting

confidence: 58%

“…Variant c.80A > G accounts for 5.95%- 9.09% in all the Chinese cblC deficiency patients (17,18), whereas in this study all seven patients carried variant c.80A > G, accounting for 57.14% (8/14) of all the mutant alleles. In addition, among five reported Chinese cases with child-and adolescence-onset cblC-associated renal disease and genetic diagnosis (10)(11)(12)(13)(14), all of them had MMACHC heterozygous variant c.80A > G (Table 2). In contrast, the most frequent damaged allele in Caucasian patients with cblC defect and renal TMA was c.271dupA (5,6).…”

Section: Discussionmentioning

confidence: 99%

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Prominent renal complications associated with MMACHC pathogenic variant c.80A > G in Chinese children with cobalamin C deficiency

et al. 2023

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ObjectiveCblC deficiency, the most common cobalamin metabolic abnormality, is caused by pathogenic variants in the MMACHC gene. The renal complications of this disease have been described only in a small number of cases. This study aimed to better delineate renal phenotype and genetic characteristics in Chinese children with cblC defect.MethodsChildren with cblC deficiency who manifested as kidney damage were enrolled. Clinical, renal pathological, and genetic data were reviewed in detail.ResultsSeven cases were enrolled. Ages at disease onset ranged from 9 months to 5 years. All patients presented with hematuria and proteinuria, and 2/7 cases presented with nephrotic syndrome. Renal dysfunction was observed in 4/7 cases. Renal biopsy was performed in 5/7 cases, and all of them had renal thrombotic microangiopathy. Macrocytic anemia was detected in all seven patients. Six out of seven cases had hypertension, and 2/7 cases presented with pulmonary hypertension. Two of them had a mild intellectual disability, and one suffered from epilepsy. Increased urine methylmalonic acid and plasma homocysteine were detected in seven cases, while two patients had normal levels of urine methylmalonic acid at the initial evaluation. After diagnosis, all seven cases were treated with hydroxocobalamin IM. Six cases were followed-up for 3–8 years. After treatments, anemia was the first to be recovered, followed by proteinuria. Renal function recovered after 1 year in two cases, whereas patient 2 progressed to stage 2 chronic kidney disease 13 years after onset. While a case presented with end-stage kidney disease because of late diagnosis, one case died 3 months after disease onset due to giving up treatment. Three MMACHC pathogenic variants c.80A > G (8/14), c.609G > A (4/14), and c.658_660delAAG (2/14) were detected in all seven children.ConclusionMMACHC variant c.80A > G may be associated with prominent renal complications in Chinese cblC patients. Macrocytic anemia and hyperhomocysteinemia are useful clues for patients with hematuria and proteinuria caused by cblC defect. The most frequent renal pathological manifestation is thrombotic microangiopathy. Early diagnosis and treatment resulted in improving renal and hematological signs.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Prominent renal complications associated with MMACHC pathogenic variant c.80A > G in Chinese children with cobalamin C deficiency

et al. 2023

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“…Compared to those patients with cblC de ciency and TMA or HUS, none of these patients had glomerular and arteriolar TMA. Immuno uorescence reports showed that our patient had both glomerular capillary wall and endomembranous IgM, IgG and C3 deposits, which were reported in the other three cblC-de cient patients with glomerular disease [5,8,10]. Glomerular capillary wall IgM deposits and endomembranous C3 were also found in patients with cblC de ciency and TMA or HUS, but no such patients had IgG deposition [1].…”

Section: Discussionmentioning

confidence: 55%

CblC Deficiency is the Cause of Persistent Proteinuria in a Young Female Ten Years After the Diagnosis of Atypical Nephropathy: A Case Report

Yang

Xiao

2023

Preprint

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Background: Cobalamin C (cblC) deficiency is the most common inborn error of cobalamin metabolism. It is caused by pathogenic variants in the MMACHC gene with varying clinical features. However, proteinuria as the primary manifestation is exceedingly rare and renal biopsy demonstrating primary glomerular pathology also is infrequent. Here we report a pediatric patient with persistent proteinuria for ten years who was ultimately diagnosed as cblC deficiency and the pathological features suggestive of mesangial proliferative glomerulonephritis. Clinical and biochemical data, as well as detailed pathological findings at diagnosis and after 10 years, were also provided. Case presentation: A 13-year-old girl with persistent proteinuria was diagnosed with atypical nephropathy for more than ten years prior. Hyperhomocysteinemia was occasionally observed for megaloblastic anemia. Further comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC). CblC deficiency was finally found to be the cause of kidney dysfunction. Hydroxocobalamin, betaine, and L-carnitine were administered. The patient achieved resolution of the MMA and homocysteinemia, but she still had persistent proteinuria. The repeated biopsy showed developed to chronicity, which indicated a poor prognosis. Conclusions: CblC deficiency should be suspected in the event of proteinuria with or without neurological symptoms. Glomerulopathy is another histopathological pattern of renal injury that is associated with cblC deficiency. The clinical manifestations are atypical, including proteinuria, hematuria and hypertension. Early detection and treatment as well as regular follow-up are important factors for a favorable prognosis

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“…15 In the treatment of MN in the nonedema stage, Professor Qinguo Hong also chose the herbs Jinyingzi (Rosae Laevigatae Fructus) and Qianshi (Euryales Semen) to strengthen the kidney and consolidate essence, which means that sufficient kidney qi ensures sealed and consolidated essence, and the essence will be controlled rather than being leaked out. 16 Professor Shili Cao also treated MN by benefiting the kidney and consolidating essence with Jinyingzi (Rosae Laevigatae Fructus) and Qianshi (Euryales Semen). 17…”

Section: Discussionmentioning

confidence: 99%

The Study on the Action Mechanism of the Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) Couplet Herbs on Membranous Nephropathy Based on Network Pharmacology

Tian

2022

Chinese medicine and natural products

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Objective Our objective was to explore the action mechanism of the Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) couplet herbs in the treatment of membranous nephropathy (MN) based on network pharmacology. Methods The active ingredients and targets of Jinyingzi (Rosae Laevigatae Fructus) and Qianshi (Euryales Semen) were screened by systematic pharmacology database and analysis platform. Online Human Mendelian Genetic database and GeneCards database were used to retrieve MN-related targets. The active ingredient-related targets and MN disease targets were introduced into Venny 2.1, and Wayne diagram was drawn. The intersection targets were the potential targets of the Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) couplet herbs in the treatment of MN. The protein interaction network of potential targets was constructed, and the core targets were screened with String platform. Metascape platform was used for functional enrichment analysis of gene ontology (GO) and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG). The “herb-active ingredient-target-pathway” networks were drawn by using Cytoscape software, and the key components, targets, and signaling pathways were screened. Results A total of 8 active ingredients and 193 related targets in Jinyingzi (Rosae Laevigatae Fructus) and Qianshi (Euryales Semen) were screened out; a total of 1,621 targets of MN disease and 105 potential targets for the treatment of MN were obtained in the treatment with Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) couplet herbs; 40 core targets were screened by protein–protein interaction network topology analysis; a total of 1,978 results were obtained by GO function enrichment analysis, and 206 signal pathways were obtained by KEGG pathway enrichment analysis and screening. The network topology analysis of “herb-active ingredient-target-pathway” showed that the key components included quercetin, kaempferol, β-sitosterol, etc.; the key targets included protein kinase Bα (AKT), mitogen-activated protein kinase 1 (MAPK1), B-cell lymphoma-2 (BCL2), prostaglandin-endoperoxide synthase 2 (PTGS2), etc.; the key pathways included advanced glycation end product/receptor of AGE signaling pathway, phosphatidyl inositol 3-kinase (PI3K)/AKT signaling pathway, MAPK signaling pathway, hypoxia-inducible factor-1 signaling pathway, Ras signaling pathway, nuclear factor kappa-B (NF-κB) signaling pathway, Toll-like receptors signaling pathway, p53 signaling pathway and vascular endothelial growth factor signaling pathway in the late stage of diabetic complications. Conclusion The Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) couplet herbs can regulate PI3K/AKT, MAPK, NF-κB signaling pathways in MN by targeting proteins of AKT1, MAPK8, PTGS2 through key components of quercetin, β-sitosterol, and kaempferol, so as to inhibit the overexpression of inflammatory factors in renal tissues, regulate inflammatory response, and improve renal function.

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Case Report: Membranous Nephropathy Secondary to Cobalamin C Disease

Cited by 5 publications

References 19 publications

Prominent renal complications associated with MMACHC pathogenic variant c.80A > G in Chinese children with cobalamin C deficiency

Prominent renal complications associated with MMACHC pathogenic variant c.80A > G in Chinese children with cobalamin C deficiency

CblC Deficiency is the Cause of Persistent Proteinuria in a Young Female Ten Years After the Diagnosis of Atypical Nephropathy: A Case Report

The Study on the Action Mechanism of the Jinyingzi (Rosae Laevigatae Fructus)–Qianshi (Euryales Semen) Couplet Herbs on Membranous Nephropathy Based on Network Pharmacology

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