congenital afibrinogenemia

Congenital afibrinogenemia is a bleeding disorder that results from a complete absence of circulating fibrinogen, a critical blood clotting protein. This condition is caused by pathogenic variants in the genes FGA, FGB, and FGG, and it is inherited in an autosomal recessive manner. It is typically identified in infancy due to abnormal bleeding episodes, although precise prevalence estimates are not well established.

The clinical picture of congenital afibrinogenemia is defined by the consistent absence of fibrinogen, resulting in abnormal bleeding that is present in all affected individuals. Characteristic features include persistent abnormal bleeding, with many patients experiencing issues such as abnormal umbilical stump bleeding, epistaxis, and prolonged bleeding following procedures like circumcision. Other less common manifestations can include subdural or epidural hemorrhage, prolonged bleeding after dental extractions, and bruising susceptibility. Not all individuals experience all features, and severity varies considerably.

Congenital afibrinogenemia arises from variants in the FGA, FGB, and FGG genes, which encode the protein fibrinogen that is essential for blood clotting. The complete absence of fibrinogen due to these genetic defects leads to a marked bleeding tendency. In this autosomal recessive disorder, an individual must inherit two mutated copies, one from each parent, to be affected. Genetic counseling is recommended for families to better understand the inheritance pattern and implications for future pregnancies.

Currently, management of congenital afibrinogenemia focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for this condition. Therapeutic strategies are personalized and may involve the use of fibrinogen replacement during bleeding episodes, along with measures to prevent bleeding complications. Management typically involves a multidisciplinary team, and patients should discuss treatment options with their healthcare team. Genetic counseling is also recommended as part of overall care.

The prognosis of congenital afibrinogenemia varies widely among affected individuals, with outcomes largely dependent on the severity of bleeding episodes and the effectiveness of prompt, supportive care. With current standards of care, many individuals manage their condition well into adulthood, although the course can be unpredictable with some patients experiencing more severe complications than others. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with bleeding disorders and to seek genetic counseling to better understand the condition and plan for the future.

Several clinical trials are currently investigating new treatment approaches for congenital afibrinogenemia. Individuals interested in learning more about ongoing studies are encouraged to search ClinicalTrials.gov or consult their care team regarding eligibility.