MedGen

Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the quality (dysfibrinogenemia; 616004) of the circulating fibrinogen or both (hypodysfibrinogenemia; see 616004). Afibrinogenemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial hemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. Menstruating women may experience menometrorrhagia. First-trimester abortion is common. Both arterial and venous thromboembolic complications have been reported (summary by de Moerloose and Neerman-Arbez, 2009). Hypofibrinogenemia is characterized by reduced amounts of immunoreactive fibrinogen. Patients are often heterozygous carriers of afibrinogenemia mutations and are usually asymptomatic. However, they may bleed when exposed to trauma or if they have a second associated hemostatic abnormality. Women may experience miscarriages. Liver disease occurs in rare cases (summary by de Moerloose and Neerman-Arbez, 2009). [from OMIM]

Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the quality (dysfibrinogenemia) of the circulating fibrinogen, or both (hypodysfibrinogenemia). Patients with dysfibrinogenemia are frequently asymptomatic, but some patients have bleeding diathesis, thromboembolic complications, or both (summary by de Moerloose and Neerman-Arbez, 2009). Reports (e.g., Haverkate and Samama, 1995) on approximately 350 families with dysfibrinogenemia revealed that approximately half of cases are clinically silent, a quarter show a tendency toward bleeding, and another quarter show a predisposition for thrombosis with or without bleeding (summary by Lefebvre et al., 2004). [from OMIM]

Systemic amyloidosis is a rare protein misfolding and deposition disorder caused by extracellular deposition of amyloid and leading to progressive organ failure. Amyloid is composed of highly organized proteinaceous, insoluble, and degradation-resistant fibrils. Hereditary systemic amyloidosis-2 (AMYLD2), resulting from mutation in the FGA gene, is the most common form of hereditary renal amyloidosis. The kidneys are the major affected organ, presenting with proteinuria. Other less frequently involved organs include liver, heart, autonomic nerve, and, rarely, peripheral nerve. A strong family history of coronary or vascular disease is also frequently seen (summary by Muchtar et al., 2021). The various forms of hereditary systemic amyloidosis that do not have peripheral neuropathy as part of the clinical syndrome have been referred to as 'Ostertag type' in reference to a German family described by Benno Ostertag (1932) in which several members died with renal amyloidosis. Since the form of hereditary amyloidosis caused by mutation in the FGA gene is the most common in Europe and has a clinical presentation with hypertension and proteinuria, Benson (2005) considered it a very good candidate for being the original amyloidosis described by Ostertag. For a discussion of genetic heterogeneity of hereditary systemic amyloidosis, see AMYLD1 (105210). [from OMIM]