Congenital afibrinogenemia
Congenital afibrinogenemia is a rare, inherited bleeding disorder characterized by a complete absence of fibrinogen, a protein essential for blood clotting. This deficiency prevents the formation of stable blood clots, leading to uncontrolled and potentially life-threatening bleeding.
Overview
Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process (coagulation). Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, in people with congenital afibrinogenemia, blood clots do not form properly, resulting in uncontrolled bleeding.
Symptoms & Clinical Features
The symptoms of congenital afibrinogenemia can range from mild to life-threatening and include:
- Prolonged bleeding from the umbilical cord stump after birth in newborns
- Nosebleeds (epistaxis) and bleeding from the gums or tongue, which can occur spontaneously or after minor trauma
- Bleeding into the spaces between joints (hemarthrosis) or into the muscles (hematoma)
- Abnormally heavy menstrual bleeding (menorrhagia) in women
- Difficulty carrying a pregnancy to term, resulting in repeated miscarriages without proper treatment
- Rarely, fatal bleeding in the brain or other internal organs
Frequency
Congenital afibrinogenemia is a rare condition that occurs in approximately 1 in 1 million newborns.
Causes & Genetics
Congenital afibrinogenemia results from mutations in one of three genes: FGA, FGB, or FGG.
Each of these genes provides instructions for making one subunit of the protein fibrinogen. This protein is critical for coagulation. In response to an injury, fibrinogen is normally converted into fibrin, the main protein in blood clots. Fibrin proteins attach to one another to form a stable network that makes up the clot.
The condition is caused by a complete absence of the fibrinogen protein. Most mutations in the FGA, FGB, and FGG genes introduce a premature stop signal in the instructions for making the protein, resulting in a nonfunctional or entirely absent subunit. If any one subunit is missing, the fibrinogen protein cannot be assembled, preventing the formation of fibrin and blood clots.
Associated Genes
- FGA
- FGB
- FGG
Inheritance Pattern
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. These carriers typically have about half the normal level of fibrinogen in their blood but do not show signs and symptoms of the condition.
Other Names for This Condition
- Afibrinogenemia
- Familial afibrinogenemia