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Genetics Home Reference: your guide to understanding genetic conditions
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Congenital afibrinogenemia

Reviewed September 2014

What is congenital afibrinogenemia?

Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding). Some affected individuals experience bleeding into the spaces between joints (hemarthrosis) or the muscles (hematoma). Rarely, bleeding in the brain or other internal organs occurs, which can be fatal. Women with congenital afibrinogenemia can have abnormally heavy menstrual bleeding (menorrhagia). Without proper treatment, women with this disorder may have difficulty carrying a pregnancy to term, resulting in repeated miscarriages.

How common is congenital afibrinogenemia?

Congenital afibrinogenemia is a rare condition that occurs in approximately 1 in 1 million newborns.

What genes are related to congenital afibrinogenemia?

Congenital afibrinogenemia results from mutations in one of three genes, FGA, FGB, or FGG. Each of these genes provides instructions for making one part (subunit) of a protein called fibrinogen. This protein is important for blood clot formation (coagulation), which is needed to stop excessive bleeding after injury. In response to injury, fibrinogen is converted to fibrin, the main protein in blood clots. Fibrin proteins attach to each other, forming a stable network that makes up the blood clot.

Congenital afibrinogenemia is caused by a complete absence of fibrinogen protein. Most FGA, FGB, and FGG gene mutations that cause this condition result in a premature stop signal in the instructions for making the respective protein. If any protein is made, it is nonfunctional. When any one subunit is missing, the fibrinogen protein is not assembled, which results in the absence of fibrin. Consequently, blood clots do not form in response to injury, leading to the excessive bleeding seen in people with congenital afibrinogenemia.

Related Gene(s)

Changes in these genes are associated with congenital afibrinogenemia.

  • FGA
  • FGB
  • FGG

How do people inherit congenital afibrinogenemia?

Congenital afibrinogenemia is inherited in an autosomal recessive pattern, 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. The parents have about half the normal level of fibrinogen in their blood but typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of congenital afibrinogenemia?

These resources address the diagnosis or management of congenital afibrinogenemia and may include treatment providers.

  • Genetic Testing Registry: Hereditary factor I deficiency disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0019250)

You might also find information on the diagnosis or management of congenital afibrinogenemia in Educational resources (http://www.ghr.nlm.nih.gov/condition/congenital-afibrinogenemia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/congenital-afibrinogenemia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about congenital afibrinogenemia?

You may find the following resources about congenital afibrinogenemia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for congenital afibrinogenemia?

  • afibrinogenemia
  • familial afibrinogenemia

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about congenital afibrinogenemia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding congenital afibrinogenemia?

autosomal ; autosomal recessive ; blood clotting ; cell ; clotting ; coagulation ; congenital ; deficiency ; factor I ; familial ; fibrin ; fibrinogen ; gene ; gums ; inherited ; injury ; protein ; recessive ; spontaneous ; subunit ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Casini A, Lukowski S, Quintard VL, Crutu A, Zak M, Regazzoni S, de Moerloose P, Neerman-Arbez M. FGB mutations leading to congenital quantitative fibrinogen deficiencies: an update and report of four novel mutations. Thromb Res. 2014 May;133(5):868-74. doi: 10.1016/j.thromres.2014.01.022. Epub 2014 Jan 25. (http://www.ncbi.nlm.nih.gov/pubmed/24560896?dopt=Abstract)
  • de Moerloose P, Casini A, Neerman-Arbez M. Congenital fibrinogen disorders: an update. Semin Thromb Hemost. 2013 Sep;39(6):585-95. doi: 10.1055/s-0033-1349222. Epub 2013 Jul 12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23852822?dopt=Abstract)
  • Lak M, Keihani M, Elahi F, Peyvandi F, Mannucci PM. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol. 1999 Oct;107(1):204-6. (http://www.ncbi.nlm.nih.gov/pubmed/10520042?dopt=Abstract)
  • Neerman-Arbez M, de Moerloose P, Bridel C, Honsberger A, Schönbörner A, Rossier C, Peerlinck K, Claeyssens S, Di Michele D, d'Oiron R, Dreyfus M, Laubriat-Bianchin M, Dieval J, Antonarakis SE, Morris MA. Mutations in the fibrinogen aalpha gene account for the majority of cases of congenital afibrinogenemia. Blood. 2000 Jul 1;96(1):149-52. (http://www.ncbi.nlm.nih.gov/pubmed/10891444?dopt=Abstract)
  • Neerman-Arbez M, de Moerloose P, Honsberger A, Parlier G, Arnuti B, Biron C, Borg JY, Eber S, Meili E, Peter-Salonen K, Ripoll L, Vervel C, d'Oiron R, Staeger P, Antonarakis SE, Morris MA. Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes. Hum Genet. 2001 Mar;108(3):237-40. (http://www.ncbi.nlm.nih.gov/pubmed/11354637?dopt=Abstract)
  • Neerman-Arbez M, Honsberger A, Antonarakis SE, Morris MA. Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia. J Clin Invest. 1999 Jan;103(2):215-8. Erratum in: J Clin Invest 1999 Mar;103(5):759. (http://www.ncbi.nlm.nih.gov/pubmed/9916133?dopt=Abstract)
  • Neerman-Arbez M. Molecular basis of fibrinogen deficiency. Pathophysiol Haemost Thromb. 2006;35(1-2):187-98. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16855369?dopt=Abstract)
  • Weisel JW. Fibrinogen and fibrin. Adv Protein Chem. 2005;70:247-99. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15837518?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2014
Published: December 16, 2014