complement factor I deficiency

Complement factor I deficiency is a very rare immunological condition that affects the complement system, an important part of the body’s defense against infections. The disorder is caused by pathogenic variants in the CFI gene, which normally helps regulate complement activity. It manifests in individuals of all ages with a broad spectrum of severity, and its extremely low prevalence means it affects fewer than 1 in 1,000,000 people. As a disorder inherited in an autosomal recessive manner, both copies of the gene must be altered for the condition to be present.

Individuals with complement factor I deficiency commonly exhibit a significantly decreased circulating concentration of complement factor I, a feature present in all affected individuals. Other clinical features observed in a subset of patients include reduced levels of complement factor B and complement C3, recurrent episodes of meningitis, septic arthritis, recurrent meningococcal disease, sinusitis, and otitis media. Not all individuals experience all these features, and severity varies considerably. These infections often prompt clinical evaluation, as the recurrent nature of these symptoms may eventually lead to the diagnosis of a complement regulation abnormality.

Complement factor I deficiency results from pathogenic variants in the CFI gene, which encodes an enzyme critical for controlling the activation of the complement system. Disruption of this gene interferes with the regulation of immune responses, making affected individuals more prone to infections. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two altered copies of the gene, one from each parent, to be affected. This condition is more common when parents share a common ancestor, as this increases the likelihood that both parents will carry the same rare variant. Genetic counseling may be valuable for families in understanding inheritance and family planning.

Currently, management focuses on supportive care and treating symptoms as they arise because there are no treatments specifically approved for complement factor I deficiency. Patients typically benefit from strategies aimed at reducing the risk and severity of infections and may require a multidisciplinary team to address complications effectively. Genetic counseling is recommended to help families understand the condition and discuss appropriate monitoring and treatment options with their healthcare team.

The outlook for individuals with complement factor I deficiency varies widely depending on the severity of the symptoms and the effectiveness of managing recurrent infections. With careful monitoring and prompt treatment of infections, many individuals are able to maintain a good quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling to understand what the diagnosis means for long-term health and family planning.

Clinical trials are underway exploring new treatment approaches for complement factor I deficiency. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about potential eligibility, as research continues to advance our understanding of this condition.