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

Abstract

Abstract 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