暂无摘要。

C3 glomerulopathy is a recently described pathological entity including dense deposit disease and C3 glomerulonephritis (C3GN). In some cases, C3 glomerulopathy is associated with defects or even complete deficiency of factor H. However, complete factor H deficiency among patients with C3GN is rare, and paediatric cases have not yet been described. Here, we report a child with homozygous factor H deficiency who presented with haematuria and minor proteinuria, together with undetectable plasma C3 levels, at the age of 10 years. Kidney biopsy demonstrated C3GN. Detailed complement analysis revealed complete factor H deficiency due to a homozygous CFH mutation. Furthermore, there was a complete deletion of CFHR-1/-3. During follow-up, the patient has had recurrent episodes of macro-haematuria and minor proteinuria, but during 4 years of follow-up, no deterioration of renal function has been observed. Mutations of factor H in C3GN have been described; however, complete CFH deficiency is rare in these patients. Furthermore, clinical presentation usually occurs in adulthood. Therefore, this case presents a rare manifestation of the disease and might contribute to the early detection of similar cases also in childhood.

BACKGROUND: Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare disease, accounting for 3-5% of all cases of primary nephritic syndrome. We report an uncommon case of familial MPGN type I associated with a new mutation in the complement factor H gene (CFH).
METHODS: Clinical data were collected on three siblings with known factor H deficiency who presented with MPGN. All underwent immunological and genetic assays. Their parents and ten healthy adults served as controls for the DNA analysis.
RESULTS: All three children presented with recurrent episodes of hematuria and proteinuria, the youngest starting at age 5 months. One child currently has nephrotic syndrome and end-stage renal disease. All of the children were found to be homozygous for a C.262C > A (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a quantitative/functional deficiency of factor H. The parents of the three siblings were found to be heterozygous for the mutation. None of the controls carried this mutation.
CONCLUSIONS: Different mutations in CFH may be responsible for different glomerular diseases, including MPGN type I. A modifier gene or an environmental trigger may contribute to this phenotype-genotype discrepancy. Understanding the role of the alternative complement pathway in this disease would allow us to offer these patients more targeted therapy, including a clinical trial of eculizumab.