Interpretive Handbook

Test 60722 :
Fibrinogen Alpha-Chain (FGA) Gene, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The systemic amyloidoses are a number of disorders of varying etiology characterized by extracellular protein deposition. The most common form is an acquired amyloidosis secondary to multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) in which the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of proteins. There are also hereditary forms of amyloidosis.


The hereditary amyloidoses comprise a group of autosomal dominant, late-onset diseases that show variable penetrance. A number of genes have been associated with hereditary forms of amyloidosis including those that encode transthyretin, apolipoprotein AI, apolipoprotein AII, gelsolin, cystatin C, lysozyme and fibrinogen alpha chain (FGA). Apolipoprotein AI, apolipoprotein AII, lysozyme, and fibrinogen amyloidosis present as non-neuropathic systemic amyloidosis, with renal dysfunction being the most prevalent manifestation.


FGA-related familial visceral amyloidosis commonly presents with renal failure, which can often be fulminant, and is characterized by hypertension, proteinuria, and azotemia. Liver and spleen involvement may be seen in advanced cases. Neuropathy is not a feature of FGA-related familial visceral amyloidosis


Due to the clinical overlap between the acquired and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and consider appropriate therapeutic interventions. Tissue-based, laser capture tandem mass spectrometry might serve as a useful test preceding gene sequencing to better characterize the etiology of the amyloidosis, particularly in cases that are not clear clinically.


It is important to note that there are rare disorders of hemostasis that are also associated with mutations in the FGA gene. Patients with afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia have all been reported to have mutations in FGA. Most dysfibrinogenemias are autosomal dominant disorders; afibrinogenemia and hypofibrinogenemia are more often autosomal recessive disorders. In general, truncating mutations in FGA result in afibrinogenemia and missense mutations are a common cause of dysfibrinogenemia.

Useful For Suggests clinical disorders or settings where the test may be helpful

Carrier testing of individuals with a family history of fibrinogen alpha-chain (FGA) gene-related familial visceral amyloidosis


Diagnostic confirmation of FGA-related familial visceral amyloidosis when familial mutations have been previously identified


Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order FGAMS / Fibrinogen Alpha-Chain (FGA) Gene, Full Gene Analysis.


Analysis is performed for the familial mutation provided only. This assay does not rule-out the presence of other mutations within this gene or within other genes that may be associated with FGA-related familial visceral amyloidosis.


We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Predictive testing of an asymptomatic child is not recommended.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Benson MD: The hereditary amyloidoses. Best Pract Res Clin Rhematol 2003;17:909-927

2. Benson MD: Ostertag revisited: The inherited systemic amyloidoses without neuropathy. Amyloid 2005;12(2):75-87

3. Asselta R, Duga S, Tenchini ML: The molecular basis of quantitative fibrinogen disorders. Thromb Haemost 2006 Oct;4(10):2115-2129

4. Shiller SM, Dogan A, Highsmith WE: Laboratory methods for the diagnosis of hereditary amyloidoses. In Amyloidosis-Mechanisms and Prospects for Therapy. Edited by S Sarantseva. InTech 2011, pp101-120