C7 Deficiency

C7 deficiency is a rare autosomal recessive terminal complement deficiency that predisposes to recurrent meningococcal and gonococcal infection.

Pathophysiology. C7 anchors the C5b6 complex to the cell membrane and lets C8 and C9 insert, so it is needed to form the membrane attack complex. In its absence, the complex is not built and Neisseria are not lysed.

Disease may start in childhood or adulthood. Most episodes are caused by uncommon serogroups, and recurrence is common without prevention.

Genetic variants are heterogeneous. Some patients also have C6 and C7 gene variants together, which can complicate testing.

• Recurrent meningococcal meningitis or septicaemia, often with uncommon serogroups
• Disseminated gonococcal infection
• Mild or atypical presentations, sometimes with little rash
• Occasional lupus like disease or vasculitis
• Some are well and found on family testing

• Total haemolytic complement (CH50) and alternative activation assay (AH50): both absent or very low.
• C7 level: absent or very low by immunoassay, with normal C3 and C4. C7 is also made in extrahepatic tissues, which can cause a low level result.
• Genetic testing of C7, and of C6 if the picture is atypical, with family testing.
• Immunoglobulins and specific antibody responses to exclude antibody deficiency.
• Microbiology and serogroup identification during infection.
• Retest after recovery from acute infection.

Differential diagnosis.

• C5, C6, C8 and C9 deficiency
• Properdin deficiency
• Acquired terminal complement inhibition (eculizumab, ravulizumab)
• Factor H and factor I deficiency
• Antibody deficiency and splenic hypofunction
• Other complement deficiencies

• Vaccination:
  • Meningococcal ACWY conjugate vaccine, 2 doses at least 8 weeks apart, then a booster every 5 years.
  • Meningococcal B vaccine, a course of 2 or 3 doses depending on the product, with boosters every 5 years.
  • Pneumococcal conjugate vaccine, then pneumococcal polysaccharide vaccine at least 8 weeks later.
  • Haemophilus influenzae type b vaccine and yearly inactivated influenza vaccine.
  • Vaccine protection is incomplete, so continue prophylaxis and fever precautions.
• Antibiotic prophylaxis: long term phenoxymethylpenicillin 250 mg orally twice daily (children under 6 years 125 mg twice daily; 6 to 11 years 250 mg twice daily), especially after a first episode of invasive disease.
• Acute fever or illness: this is possible meningococcal disease. After blood cultures, give ceftriaxone 2 g intravenously once daily (children 50 to 80 mg/kg, maximum 2 g) without waiting for results, and admit. Give the family an emergency card.
• Contacts of an invasive case: ciprofloxacin as a single oral dose of 500 mg in adults (children 5 to 12 years 250 mg; 1 month to 4 years 30 mg/kg, maximum 125 mg), or rifampicin 600 mg twice daily for 2 days in adults.
• Lupus like disease or vasculitis, if it occurs: hydroxychloroquine 200 to 400 mg orally daily, not over 5 mg/kg of actual body weight daily, and prednisolone 0.5 to 1 mg/kg daily (maximum 60 mg), tapered.
• Fresh frozen plasma is not used routinely.

Special groups.

• Relatives: test siblings, since each has a 1 in 4 risk of being affected.
• Adolescents: confirm boosters and the emergency plan at transition to adult care.

Monitoring. Clinical review every 6 to 12 months. Vaccine booster record every 5 years. Confirm adherence to prophylaxis.

Referral and escalation. Refer to immunology after any second episode of meningococcal disease, an uncommon serogroup, or disseminated gonococcal infection. Emergency for fever with rash, headache, vomiting or drowsiness.