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. Associated genes include CFI.