Complement Factor D Deficiency D81.4

Complement factor D deficiency is an autosomal recessively inherited immunological defect characterized by increased susceptibility to bacterial infections, particularly Neisseria infections.

The cause of complement factor D deficiency is a mutation in the CFD gene (134350). The CFD gene encodes a member of the S1 or chymotrypsin family of serine peptidases (serine protease). This protease catalyzes the cleavage of factor B when complexed with factor C3b. In a 2nd step, the C3bbb complex is activated, which then becomes the C3 convertase of the alternative pathway. Its function is homologous to that of C1s in the classical pathway. The mutation leads to a defect in the alternative complement pathway. (Biesma et al. 2001).

Biesma et al (2001) reported a 23-year-old female patient born to consanguineous parents who had septic shock due to Neisseria meningitidis in blood and CSF. A deceased family member suffered from recurrent bacterial meningitis. Lab: complete absence of factor D activity. Absence of factor D activity was also found in three family members who were asymptomatic. Apparently, factor D deficiency predisposes to invasive meningococcal disease (see Neisseria meningitidis below). None of the reported patients were obese (Hiemstra et al. 1989).

Sprong et al (2006) reported a Turkish sibling with invasive meningococcal disease. The 19-month-old girl was admitted with purpura fulminans/ ecchymoses and sugillations/high fever, cough, diarrhea, and vomiting. Lab: N. meningitidis was detected in cerebrospinal fluid cultures.

Approximately 47 hours after admission to the hospital, she died of refractory shock. Four years later, the 13-month-old brother became ill with sudden-onset fever and that was accompanied by petechial exanthema. N. meningitidis was detected in blood cultures. Lab: Complete absence of factor D. Therapy: Antibiotic prophylaxis/vaccination against N. meningitidis.

1. Barratt J et al (2021) Complement Factor D as a Strategic Target for Regulating the Alternative Complement Pathway. Front Immunol 12:712572.
2. Biesma DH et al (2001) A family with complement factor D deficiency. J Clin Invest 108: 233-240.
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4. Hiemstra PS et al (1989) Complete and partial deficiencies of complement factor D in a Dutch family. J Clin Invest 84: 1957-1961.
5. Kluin-Nelemans HC et al (1984) Functional deficiency of complement factor D in monozygous twin. Clin Exp Immun 58: 724-730.
6. Sprong T et al (2006) Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood 107: 4865-4870.