关键词: C3肾小球病, 补体, 预后, 儿童

Abstract:

Objective To investigate the clinical phenotypes, pathological characteristics, genetic variants, and treatment outcomes in children with C3 glomerulopathy (C3G), and to provide evidence for precise diagnosis and management. Methods Clinical, pathological, and genetic data from four pediatric patients diagnosed with C3G at the Department of Nephrology between July 2021 and March 2024 were retrospectively analyzed. Additionally, published cases of C3G in Chinese children from both domestic and international literature were systematically reviewed and summarized to contextualize our findings. Results Four pediatric patients with C3G were included in the study, comprising two boys and two girls aged 10 to 12 years. All presented with nephrotic syndrome and hematuria, and three exhibited renal insufficiency at initial presentation. Laboratory evaluation revealed reduced serum complement C3 levels (0.9-1.8 g/L) in all patients, decreased C4 in two, and elevated membrane attack complex (C5b-9) in all. Renal histopathology demonstrated diffuse mesangial cell and matrix proliferation in all cases. Immunofluorescence showed predominant C3 deposition, and electron microscopy confirmed a diagnosis of C3 glomerulonephritis (C3GN) in three patients and dense deposit disease (DDD) in one. Whole exome sequencing was performed in three patients, identifying a single missense variant in the C3 gene (c.4887G>C, p.Glu1629Asp) inherited from a phenotypically healthy mother; this variant was classified as having uncertain clinical significance according to ACMG criteria. All patients received immunosuppressive therapy combining glucocorticoids with other agents; eculizumab was added in two refractory cases. With follow-up of 3 to 8 months, all three patients with initial renal insufficiency achieved normalization of renal function, and proteinuria decreased in all four. Two patients attained complete remission, one achieved partial remission, and one showed no response. Conclusions Pediatric C3G predominantly manifests as nephrotic syndrome with persistent hypocomplementemia. Key pathological features include diffuse mesangial proliferation and dominant C3 deposition on immunofluorescence. Genetic variants are infrequently detected, suggesting potential non-monogenic mechanisms in many cases. Immunosuppressive regimens based on glucocorticoids remain the mainstay of therapy, while eculizumab may offer therapeutic benefit in selected refractory cases. Early integration of renal biopsy, complement profiling, and genetic analysis facilitates timely and accurate diagnosis. Long-term outcomes require further assessment through extended follow-up and larger cohort studies.

Key words: C3 glomerulopathy, complement, prognosis, child