What are the key symptoms that might indicate complement factor I deficiency, prompting a diagnostic workup?

Individuals with complement factor I deficiency often experience recurrent infections, particularly of the upper respiratory tract, ears, skin, and urinary tract. More severe infections like pneumonia, meningitis, or sepsis can also occur and may be life-threatening. Some people may also develop a specific kidney disorder called glomerulonephritis or autoimmune conditions like rheumatoid arthritis or systemic lupus erythematosus. A history of frequent or unusually severe infections, especially in childhood, should raise suspicion.

What is the genetic inheritance pattern of complement factor I deficiency, and how does it affect family members?

Complement factor I deficiency is typically inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated CFI gene (one from each parent) to develop the condition. Parents who each carry one copy of the mutated gene are usually healthy themselves but have a 25% chance with each pregnancy of having a child with the deficiency. Genetic counseling is recommended for affected individuals and their families to understand inheritance risks and testing options.

How is complement factor I deficiency typically managed to prevent severe infections and other complications?

Management primarily focuses on preventing and promptly treating infections. This often involves prophylactic antibiotics to reduce the frequency of bacterial infections, and vaccinations to protect against common pathogens. Regular monitoring for kidney function and signs of autoimmune disease is also crucial. In some cases, infusions of fresh frozen plasma or purified complement factor I may be considered to supplement the deficient protein.

Complement factor I deficiency

Complement factor I deficiency is a rare genetic disorder that impairs the immune system, causing recurrent infections and increasing the risk of autoimmune diseases. The condition results from mutations in the CFI gene, leading to uncontrolled activation of the complement system.

Overview

Complement factor I deficiency is a disorder that affects the immune system. People with this condition are prone to recurrent infections, including infections of the upper respiratory tract, ears, skin, and urinary tract. They may also contract more serious infections such as pneumonia, meningitis, and , which may be life‑threatening.

Some people with complement factor I deficiency have a kidney disorder called glomerulonephritis with isolated C3 deposits. Complement factor I deficiency can also be associated with autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus (SLE). Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs.

Frequency

Complement factor I deficiency is a rare disorder; its exact prevalence is unknown. At least 38 cases have been reported in the medical literature.

Causes & Risk Factors

Complement factor I deficiency is caused by mutations in the CFI gene. This gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the . The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger , and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed.

Mutations in the CFI gene that cause complement factor I deficiency result in abnormal, nonfunctional, or absent complement factor I. The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. In addition, the immune system may malfunction and attack its own tissues, resulting in autoimmune disorders.

Learn more about the gene associated with Complement factor I deficiency

Inheritance

This condition is inherited in an , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

C3 inactivator deficiency
Complement component 3 inactivator deficiency
Hereditary factor I deficiency disease

Additional Information & Resources

Genetic Testing Information

Genetic Testing Registry: Hereditary factor I deficiency disease

Patient Support and Advocacy Resources

National Organization for Rare Disorders (NORD)

Clinical Trials

ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

COMPLEMENT FACTOR I DEFICIENCY; CFID

Scientific Articles on PubMed

PubMed

References

Baracho GV, Nudelman V, Isaac L. Molecular characterization of homozygous hereditary factor I deficiency. Clin Exp Immunol. 2003 Feb;131(2):280-6. doi: 10.1046/j.1365-2249.2003.02077.x. Citation on PubMed or Free article on PubMed Central
Grumach AS, Leitao MF, Arruk VG, Kirschfink M, Condino-Neto A. Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family. Clin Exp Immunol. 2006 Feb;143(2):297-304. doi: 10.1111/j.1365-2249.2005.02988.x. Citation on PubMed or Free article on PubMed Central
Nilsson SC, Trouw LA, Renault N, Miteva MA, Genel F, Zelazko M, Marquart H, Muller K, Sjoholm AG, Truedsson L, Villoutreix BO, Blom AM. Genetic, molecular and functional analyses of complement factor I deficiency. Eur J Immunol. 2009 Jan;39(1):310-23. doi: 10.1002/eji.200838702. Citation on PubMed
Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann N Y Acad Sci. 2009 Sep;1173:108-23. doi: 10.1111/j.1749-6632.2009.04633.x. Citation on PubMed
Ponce-Castro IM, Gonzalez-Rubio C, Delgado-Cervino EM, Abarrategui-Garrido C, Fontan G, Sanchez-Corral P, Lopez-Trascasa M. Molecular characterization of Complement Factor I deficiency in two Spanish families. Mol Immunol. 2008 May;45(10):2764-71. doi: 10.1016/j.molimm.2008.02.008. Epub 2008 Mar 28. Citation on PubMed
Vyse TJ, Morley BJ, Bartok I, Theodoridis EL, Davies KA, Webster AD, Walport MJ. The molecular basis of hereditary complement factor I deficiency. J Clin Invest. 1996 Feb 15;97(4):925-33. doi: 10.1172/JCI118515. Citation on PubMed or Free article on PubMed Central
Vyse TJ, Spath PJ, Davies KA, Morley BJ, Philippe P, Athanassiou P, Giles CM, Walport MJ. Hereditary complement factor I deficiency. QJM. 1994 Jul;87(7):385-401. Citation on PubMed

Medical Encyclopedia Topics

Complement
Genetics
Immunodeficiency diseases

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