In consequence, liver cells, the normal site of fibrinogen production, make small amounts of this critical coagulation protein, blood levels of fibrinogen are low, and individuals with the disorder may develop a coagulopathy, i.e. a diathesis or propensity to experience episodes of abnormal bleeding.
[1][2] Certain gene mutations causing congenital hypofibrinogenemia disrupt the ability of liver cells to secrete fibrinogen.
Those with particularly low blood fibrinogen levels (<0.5 gram/liter) may develop serious bleeding spontaneously and many with the disorder do so following trauma or surgery.
Depending on their fibrinogen levels, women with the disorder may also bleed excessively during delivery and the postpartum period; in rare cases, they may have an increased risk of suffering miscarriages.
[1][4][5] Individuals with the disorder also experience thrombotic events which may include blockage of large arteries in relatively young patients who have high levels of cardiovascular risk factors.
Unlike other forms of congenital hypofibrinogenemia, a relatively high percentage of individuals with fibrinogen storage disease have been diagnosed in children of very young age.
[8][9] The genes are ordered FGB, FGA, and FGG and are transcribed into messenger RNA in tight synchrony.
The assembled protein is passes to the Golgi apparatus where it is glycosylated, hydroxylated, sulfated, and phosphorylated to form the mature fibrinogen glycoprotein that is secreted into the blood.
The diagnosis of hypofibrinogenemia is indicated in individuals who have low levels (<1.5 gram/liter) of plasma fibrinogen as determined by both immunological (e.g. immunoelectrophoresis and (i.e. able to be clotted) methods.
[11] The diagnosis of fibrin storage disease requires liver biopsy and the finding of immunologically detectable fibrinogen inclusion bodies in hepatocytes.
[3] Recommended treatment of asymptomatic congenital hypofibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as indicated by the personal history of the affected individual and family members.
In the latter disease, autophagy, the pathway that cells use to dispose of dysfunctional or excessively stored components including proteins, has been targeted using autophagy-enhancing drugs, e.g. carbamazepine, vitamin E, and ursodeoxycholic acid.