Membranoproliferative glomerulonephritis associated with hereditary deficiency of the 4th component of complement.

A 10-year-old female patient was found positive for urine protein and occult blood on Japanese school urinary screening. Examination of the blood was normal except low values of the complement system with CH50 13.5 U/ml, C3 45 mg/dl and C4 3 mg/dl. Renal biopsy demonstrated a focal membranoproliferative glomerulonephritis (MPGN). As for the activity of each component of the complement in the early stage of the disease, the C4 activity was markedly declined and the activity of classical pathway component was also decreased, but the activity of alternative pathway component was normal. On the HLA examination, the patient demonstrated a C4 double null haplotype (C4A2, Q0, BQ0 phenotype). A null C4 gene at both the C4A and C4B loci was found in her mother, aunt and grandfather on the mother's side and C4B null allele in her father and her grandmother on the mother's side. The development of the disease is found in 1 case and not in the other, although both have the genetic defect and the mechanism by which the complement is activated remains unknown. Thus, there appear to be many subjects to be studied as to the relationship between the defect of C4 gene and immune competence.