Late-onset Renal involvement presenting with TMA and tubular injury in cobalamin C disease: a report of three cases and review of the literature

Abstract

Abstract Background: Mutation of methylmalonic aciduria type C and homocystinuria (MMACHC) gene causes inherited cobalamin C disease (cblC), an inborn error of cobalamin metabolism, which presents with methylmalonic aciduria (MMA) and homocystinuriain clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is presented with thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported.This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists. Case presentation: Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealed elevated serum and urine homocysteine, renal biopsy showed TMA and tubular injury, along with genetic testing showing a heterogeneous compound mutation of MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered, ranging from recovery of kidney function to kidney failure. Conclusions: The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease.