complement component 3 deficiency

Complement component 3 deficiency is a rare genetic disorder that affects the body’s immune system, resulting in an increased vulnerability to infections and immune complex diseases. It is caused by ineffective or decreased production of the C3 protein due to pathogenic variants in the C3 gene. The inherited form of this condition typically presents in the first decade of life with recurrent bacterial infections, tonsillitis, fever, and signs of autoimmunity such as systemic lupus erythematosus. This condition is very rare, affecting fewer than 1 in a million individuals.

Individuals with complement component 3 deficiency characteristically have decreased levels of circulating complement C3, which is essential for an effective immune response. Clinically, affected children experience recurrent bouts of tonsillitis, pneumonia, and other bacterial infections, in addition to recurrent fevers, and they may also develop manifestations of immune complex diseases such as systemic lupus erythematosus. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the C3 gene, which leads to reduced production or function of the C3 protein, a key component of the complement system that helps the body fight infections. It is inherited in an autosomal recessive pattern, which means that an affected individual inherits one defective copy of the gene from each parent. This condition is more common when parents share a common ancestor because the likelihood of both carrying the same rare genetic variant increases. Families may benefit from genetic counseling to further understand the inheritance and implications for family planning.

Currently, management of complement component 3 deficiency focuses on supportive care and symptom control, as there are no therapies specifically approved for this condition. Treatment is tailored to the individual's needs, with management plans that may include prompt antibiotic intervention during infections and strategies to manage immune complex-mediated complications. Patients are typically followed by a multidisciplinary team, and further management decisions should be made in consultation with their healthcare providers. Genetic counseling is also recommended to help families understand the condition and to discuss family planning options.

The clinical course of complement component 3 deficiency can vary significantly between individuals. Many affected persons experience recurrent infections and immune-related complications during childhood, with outcomes that depend on the severity of the immune deficiency and the timeliness of medical interventions. With current standards of care and ongoing advancements in supportive therapies, outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists experienced in immunodeficiency disorders and genetic counseling to discuss individual prognosis and ongoing management.

Clinical trials are underway exploring new treatment approaches for complement component 3 deficiency. Although there are currently no therapies specifically approved for this condition, ongoing research efforts are aimed at better understanding the disorder and developing targeted interventions. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about potential eligibility for emerging treatments.