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. Congenital hypfibrinogenemia results from inherited mutations in one of the three fibrinogen chains that results in the disruption of fibrinogen synthesis, assembly, stability, processing through the endoplasmic reticulum-Golgi apparatus pathway, and/or secretion into the blood.There are >25 fibrinogen mutations that have been associated with hypofibrinogenemia. The following Table lists examples of those mutations which cause hypofibrinogenemia that is not associated with liver injury. The Table gives: a) each mutated proteins trivial name; b) the gene mutated (i.e. FGA, FGB, or FGG), its mutation site (i.e. numbered nucleotide in the gene beginning with the initial nucleotide base at the (start codon) of genomic DNA (as indicated by the "g." notation), and name of the nucleotides (i.e. C, T, A, G) at these sites before>after the mutation; and c) the name of the altered fibrinogen peptide (Aα, Bβ, or λ), the numbered position(s) of the amino acid changed by the mutation in the circulating peptide of the mutated fibrinogen, and the identity of the amino acids before-after the mutation using standard three letter abbreviations. In the Table, fs indicates a mutation that causes a Translational frameshift and consequently a premature stop codon (designated by "X") mutation and translation of a shortened fibrinogen chain, del is a deletion, and ins is an insertion.
Immunological/functional fibrinogen ratios for the plasma of individuals with hypodysfibrinogenemia for all the cited tests are usually <0.7. Where available, further analyses are recommended; these include analyses of the fibrinogen genes and protein chains for mutations and specialized studies of individuals in vitro induced blood clots for stability and susceptibility to lyses.The diagnosis of fibrin storage disease requires liver biopsy and the finding of immunologically detectable fibrinogen inclusion bodies in hepatocytes. Treatment
No symptoms
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. Where possible, determination of the exact mutation causing the disorder and the propensity of this mutation type to develop these complications may be helpful. Individuals with fibrinogen levels >1.0 gram/liter typically do not develop bleeding or thrombosis episodes. Individuals with fibrinogen levels of 0.5-1.0 grams/liter require  fibrinogen supplementation preferably with a plasma-derived fibrinogen concentrate to maintain fibrinogen levels of >1 gram/liter prior to major surgery. Individuals with fibrinogen levels of <0.5 gram/liter require fibrinogen supplementation to maintain fibrinogen levels of a) >1 to 2 gram/liter at the end of pregnancy and during the postpartum period; b) > 1 gram/liter prior to major surgery; c) > 0.5 to 1 gram/liter during the first two trimesters of pregnancy; and d) >0.5 gram/liter prior to minor surgery. Tranexamic acid may be used in place of fibrinogen supplementation as prophylactic treatment prior to minor surgery and to treat minor bleeding episodes.