Complement factor I deficiency D81.4

Immunodeficiency with factor I abnormality (OMIM: 610984) is a rare, genetic, autosomal recessive, primary immune deficiency disease characterized by increased susceptibility to recurrent, usually severe, infections (particularly by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae). The immunodeficiency typically manifests as bacterial otitis, sinusitis, bronchitis, pneumonia, and/or meningitis. It is caused by mutations in the CFI gene.

Autoimmune diseases (e.g., systemic lupus erythematosus, C3 glomerulonephritis) and atypical hemolytic uremic syndrome may also be associated with this complement defect. Laboratory analysis of serum shows decreased or undetectable complement factor I as well as varying degrees of decreased complement C3, complement factor B, and complement factor H.

Grumach et al (2006) reported on a large consanguineous Brazilian family in which 3 individuals had complete factor I deficiency and another 16 individuals had partial factor I deficiency. The individuals with complete deficiency had recurrent respiratory infections, skin infections, and meningitis; one individual died of sepsis. All patients had low serum C3, decreased factor H, and undetectable factor I activity. Of the patients with partial factor I deficiency, 10 suffered from recurrent infections such as tonsillitis, pneumonia, urinary tract infections, otits media, and meningitis. One subject each had chronic arthritis and rheumatic fever. Two subjects with partial deficiency were clinically healthy. It is likely that factor I deficiency partially impairs clearance of immune complexes by phagocytes, increasing the risk for development of immune complex-mediated diseases. Prophylactic vaccination therapy is recommended.

Sadallah et al (1999) reported a patient with complement factor I deficiency who had suffered from recurrent otitis, sinusitis, and bronchopneumonia since childhood. At the age of 24 years, he was diagnosed with immune complex vasculitis of the skin (purpura). Other complement components in the serum, especially C3 were decreased (this explains the predisposition to bacterial infections). At 40 years of age, signs of progressive renal insufficiency (accompanied by proteinuria and hematuria). Biopsy shows focal segmental glomerulonephritis with glomerular deposits of immunoglobulins and C3 and C4.

Servais et al (2007) described patients with factor I deficiency as well as "C3 glomerulonephritis " (mesangial C3 deposits). Heterozygous mutations in complement regulatory genes were identified in 4 of 6 unrelated patients with C3 glomerulonephritis, including 2 patients each with mutations in the CFH and CFI genes. The results suggest that dysregulation of the alternative complement pathway is associated with a broad spectrum of diseases ranging from atypical hemolytic uremic syndrome (aHUS; 235400) to glomerulonephritis with C3 deposits.

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