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Disease Profile

Afibrinogenemia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

0

US Estimated

Europe Estimated

Age of onset

Infancy

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ICD-10

D68.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Afibrinogenemia congenital; Congenital afibrinogenemia

Categories

Blood Diseases; Congenital and Genetic Diseases

Summary

Afibrinogenemia, sometimes called congenital afibrinogenemia, is an inherited blood disorder in which the blood does not clot normally. It occurs when there is a lack (deficiency) of a protein called fibrinogen (or coagulation factor I), which is needed for the blood to clot.[1][2] Affected individuals may be susceptible to severe bleeding (hemorrhaging) episodes, particularly during infancy and childhood. Afibrinogenemia is thought to be transmitted as an autosomal recessive trait.[2] Treatment may include cryoprecipitate (a blood product containing concentrated fibrinogen and other clotting factors), fibrinogen concentrates or plasma (the liquid portion of the blood which contains clotting factors).[1]

 

Symptoms

In afibrinogenemia, with fibrinogen levels less than 0.1 g/L, bleeding abnormalities range from mild to severe. Bleeding from the umbilical cord just after birth frequently provides an early alert to the abnormality. Other symptoms include the following:[1][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Epistaxis
Bloody nose
Frequent nosebleeds
Nose bleed
Nose bleeding
Nosebleed

[ more ]

 0000421
Gingival bleeding
Bleeding gums
0000225
Joint swelling
0001386
Menometrorrhagia
0400008
Spontaneous abortion
0005268
5%-29% of people have these symptoms
Cerebral hemorrhage
Bleeding in brain
0001342
Percent of people who have these symptoms is not available through HPO
Abnormal bleeding
Bleeding tendency
0001892
Autosomal recessive inheritance
0000007
Hypofibrinogenemia
0011900
Splenic rupture
Ruptured spleen
0012223

Cause

Afibrinogenemia is caused by a severe lack of fibrinogen (coagulation factor I), a protein in the blood that is essential in the blood clotting (coagulation) process.[1][2][3] This defect in fibrinogen synthesis can result from mutations in one or another of the fibrinogen genes alpha (FGA), beta (FGB) or gamma (FGG).[3][4] Each of these three genes provides instructions for making one part (subunit) of the fibrinogen protein. When an injury occurs, 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. If there is a mutation in the FGA, FGB or FGG gene, the respective subunit is not made and the fibrinogen protein cannot be assembled. This results in the absence of fibrin, so blood clots cannot form, leading to the excessive bleeding seen in people with afibrinogenemia.[5]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no known prevention or cure for afibrinogenemia.[1] To treat bleeding episodes or to prepare for surgery to treat other conditions, patients may receive:[1][3]

    • Cryoprecipitate (a blood product containing concentrated fibrinogen and other clotting factors)
    • The liquid portion of the blood containing clotting factors (plasma)
    • Fibrinogen concentrates

    Prophylactic therapy should also be considered for patients with recurrent bleeding episodes, CNS hemorrhage, or during pregnancy for women with recurrent miscarriage.[3]

    Individuals with afibrinogenemia should consider the following as part of their management plan:

    • Consultation with a hematologist/hemostasis specialist, particularly for patients who require fibrinogen replacement therapy.[3]
    • Genetic counseling and family studies, especially for individuals with extensive family history or those considering pregnancy.[3]
    • Follow-up by a comprehensive bleeding disorder care team experienced in diagnosing and managing inherited bleeding disorders.[3]
    • Vaccination with the hepatitis B vaccine because transfusion increases the risk of hepatitis.[1]

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Human fibrinogen(Brand name: FIBRYGA) Manufactured by Octapharma
      FDA-approved indication: FIBRYGA is a human fibrinogen concentrate indicated for the treatment of acute bleeding episodes in adults and adolescents with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. FIBRYGA is not indicated for dysfibrinogenemia.
    • Human fibrinogen concentrate, pasteurized(Brand name: RiaSTAP®) Manufactured by CSL Behring, LLC
      FDA-approved indication: Treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency (afibrinogenemia and hypofibrinogenemia).
      National Library of Medicine Drug Information Portal

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Afibrinogenemia. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Afibrinogenemia. Click on the link to view a sample search on this topic.

          References

          1. Chen YB, Zieve D. Congenital afibrinogenemia. MedlinePlus. January 27, 2015; https://www.nlm.nih.gov/medlineplus/ency/article/001313.htm.
          2. Afibrinogenemia, Congenital. National Organization for Rare Disorders (NORD). 2007; https://rarediseases.org/rare-diseases/afibrinogenemia-congenital/.
          3. Acharya SS. Inherited Abnormalities of Fibrinogen. Medscape Reference. November 18, 2014; https://emedicine.medscape.com/article/960677-overview.
          4. Afibrinogenemia, Congenital. Online Mendelian Inheritance in Man (OMIM). September 22, 2014; https://omim.org/entry/202400.
          5. Congenital afibrinogenemia. Genetics Home Reference (GHR). September 2014; https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia.
          6. Familial afibrinogenemia. Orphanet. October 2009; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98880.
          7. Abolghasemi H, Shahverdi E. Umbilical bleeding: a presenting feature for congenital afibrinogenemia.. Blood Coagul Fibrinolysis. 2015 Oct; 26(7):834-5. https://www.ncbi.nlm.nih.gov/pubmed/26407137.

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