Complement system deficiencies [41 genes]

Defects in components of the complement system increase susceptibility to infections and risk of autoimmune disorders, while defects in the complement regulatory proteins can lead to serious disorders due to immune overactivation.
The clinical manifestation of these deficiencies is variable and depends on the function of the affected component in defense and inflammation.
The clinical characteristics of each pathology reflect the known functions of the complement:

• Prevention of infection
• Elimination of apoptotic cells and immune complexes
• Protection of endothelial surfaces

• ~1-10% of PIDs
• 0,03% in general population

• Diagnosis and genetic counseling
• Vaccination against encapsulated bacteria
• Antibiotics
• Anti-inflammatory therapy

Identifying a genetic defect responsible for the disease would allow a precise molecular diagnosis to be issued and make it possible to provide genetic counseling to the patient and their family members. In some cases, detecting a genetic variant can help explore specific treatment options.

Complement deficiency can lead to different diseases depending on the type of deficiency and complement factor involved:

• The complete deficiency of any of the complement factors, depending on whether it is part of the classic, alternative, or lectin pathway, can cause susceptibility to various types of infections.
• When the alteration affects complement regulators, or there is an increase in central factors consumption such as C3 or C4, there may be an increased risk of suffering from glomerular diseases (aHUS, DDD, C3G) or autoimmune diseases (SLE).
• There are some genes whose defects may be phenocopies of complement system alterations, so their study is useful as differential diagnoses.

In case of clinical suspicion and alteration of complement factors, the genetic study of this panel would be recommended.