Both disorders involve the circulation of dysfunctional fibrinogen but in congenital hypodysfibrinogenemia plasma fibrinogen levels are low while in congenital dysfibrinogenemia they are normal. Furthermore, the two disorders involve different gene mutations and inheritance patterns as well as somewhat different symptoms. Fibrinogen
Fibrinogen is a glycoprotein made and secreted into the blood primarily by liver hepatocyte cells. Endothelium cells also make what appears to be small amounts of fibrinogen but this fibrinogen has not been fully characterized; blood platelets and their precursors, bone marrow megakaryocytes, although once thought to make fibrinogen, are now known to take up and store but not make the glycoprotein. The final secreted, hepatocyte-derived glycoprotein is made of two trimers each of which is composed of three polypeptide chains, Aα (also termed α) encoded by the FGA gene, Bβ (also termed β) encoded by the FGB gene, and γ encoded by the FGG gene. All three genes are located on the long (i.e. "p") arm of human chromosome 4 (at positions 4q31.3, 4q31.3, and 4q32.1, respectively) and may contain mutations that are the cause of congenital dysfibrinogenemia. The heximer is assembled as a protein in the endoplasmic reticulum of hepatocytes and then transferred to the Golgi where Polysaccharides (i.e. complex sugars) and sialic acid are added by respective glycosylation and sialylation enzyme pathways thereby converting the heximer to a functional fibrinogen glycoprotein.
Genetic and protein analyses can definitively differentiate the two disorders. Treatment
In a study of 189 individuals diagnosed with congenital dysfibrinogenemia, ~33% were asymptomatic, ~47% experienced episodic bleeding, and ~20% experienced episodic thromboses. Due to the rareness of this disorder, treatment of individuals with these presentations are based primarily on case reports, guidelines set by the United Kingdom, and expert opinions rather than controlled clinical studies. Asymptomatic individuals
Treatment of asymptomatic congenital dysfibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as estimated based on the history of family members with the disorder and, where available, determination of the exact mutation causing the disorder plus the propensity of the particular mutation type to develop these complications. In general, individuals with this disorder require regular follow-up and multidiscipline management prior to surgery, pregnancy, and giving childbirth. Women with the disorder appear to have an increased rate of miscarriages and all individuals with fibrinogen activity in clotting tests below 0.5 grams/liter are prone to bleeding and spontaneous abortions. Women with multiple miscarriages and individuals with excessively low fibrinogen activity levels should be considered for prophylaxis therapy with fibrinogen replacement during pregnancy, delivery, and/or surgery. Symptomatic individuals
Individuals experiencing episodic bleeding as a result of congenital dysfibrinogenemia should be treated at a center specialized in treating hemophilia. They should avoid all medications that interfere with normal platelet function.