Combined homozygous factor H and heterozygous C2 deficiency in an Italian family

Abstract

Three of four children in a family have homozygous (less than 1% of normal) deficiency of factor H of the complement system and both parents, who are first cousins, are heterozygous for the same defect. The father and two of the H-deficient siblings also have a partial C2 deficiency. One of the children with combined deficiencies is affected by systemic lupus erythematosus with nephritis. No increased susceptibility to infections has been observed in the family. H deficiency is inherited in an autosomal codominant manner and is independently transmitted from C2 deficiency and HLA haplotypes. In the homozygous state it is associated with very low serum concentrations of B and C3, barely demonstrable as activated molecules. C5 is greatly reduced (less than 5%). Also, properdin and C6-9 are decreased. The findings in this family demonstrate that the occurrence of systemic lupus erythematosus in one of the children affected by a combined deficiency of factor H and C2 raises the question whether this pathology is related to the complete factor H or to the heterozygous C2 deficiency. Complete H deficiency is not necessarily accompanied by overt illness.

Heterozygous and homozygous factor H deficiency states in a Dutch family

“…Homozygous factor H deficiency in the 15 persons reported is associated with meningococcal disease, glomerulonephritis, HUS and SLE [7,[17][18][19][20][21][22][23]. Our patient had had meningococcal disease, and although the autoantibodies against ANA and dsDNA were only transiently positive, the clinical presentation and course of the dermatologic symptoms strongly suggest SCLE.…”

“…So far, 15 persons with factor H deficiency have been reported [7,[17][18][19][20][21][22][23]. Among those studied by Western blotting for the presence of the 150-kD factor H protein, small amounts of normal factor H or mutant forms were always found (Dominguez and Misiano, unpublished results).…”

“…was present. A factor H combined with heterozygosity for C2 deficiency has been described in an Italian family [18].…”

“…Homozygous deficiency of factor H has been reported in 15 subjects belonging to seven families [7,[17][18][19][20][21][22][23]. Among these 15 individuals, three suffered from meningococcal infections [17,19], nine had had glomerulonephritis [17,18,[20][21][22], two had a haemolytic uraemic syndrome (HUS) [7,23], one had asthma and one person, who was heterozygous C2-deficient as well, suffered from systemic lupus erythematosus (SLE) [18].…”

“…Among these 15 individuals, three suffered from meningococcal infections [17,19], nine had had glomerulonephritis [17,18,[20][21][22], two had a haemolytic uraemic syndrome (HUS) [7,23], one had asthma and one person, who was heterozygous C2-deficient as well, suffered from systemic lupus erythematosus (SLE) [18]. Only three deficient persons, one of whom was 3 years old at the time of the report, were healthy [7,18]. Additionally, six presumed heterozygous factor H-deficient persons were identified in three more unrelated families suffering from primary IgA nephropathy, haemolytic uraemic syndrome or Henoch-Schönlein purpura [24,25].…”