Fibrinogen A alpha-chain associated amyloidosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]
Synonyms and keywords:Fibrinogen amyloidosis
Overview
Fibrinogen A a-chain amyloidosis (AFib) is a systemic disease caused by extracellular deposition of insoluble amyloid fibrils composed of abnormal fibrinogen, arising from autosomal dominant mutations in the gene encoding AFib.
Historical Perspective
Fibrinogen A a-chain amyloidosis (AFib) was first discovered by Merill Benson et al., in 1993.[1]
Classification
- There is no established system for the classification of fibrinogen Aα-chain amyloidosis.
- However, the disease is caused by the extracellular deposition of amyloid fibrils induced by mutations in fibrinogen Aα-chain gene (FGA).[2]
- Fibrinogen Aα-chain amyloidosis may be classified according to the mutations. To date, around 16 amyloidogenic FGA mutations have been identified.[3]
Pathophysiology
- Fibrinogen A a-chain amyloidosis is a systemic amyloid disease with multivisceral and neurologic involvement, and is associated with cardiac amyloid deposition, amyloid angiopathy, and atheromatosis.
- Fibrinogen is a plasma protein with a crucial role in the coagulation cascade through its conversion to fibrin.
- Fibrinogen composed of 2 identical sets of 3 polypeptide chains termed A α, B β, and γ, joined by disulfide bridging.
- Each polypeptide is encoded by a distinct gene, FGA, FGB, and FGG.
- The gene for the fibrinogen A α-chain with 610 amino acid residues is localized on chromosome 4 and has 6 exons.[4]
- Mutations in any of the 3 genes encoding for fibrinogen polypeptides can cause dysfibrinogenemias, coagulation disorders caused by a variety of structural abnormalities in the fibrinogen molecule that result in abnormal fibrinogen function.
- Recently identified mutations in the A α-chain gene can lead to hereditary systemic amyloidosis.[5]
Causes
Fibrinogen Aα-chain amyloidosis is caused by the extracellular deposition of amyloid fibrils induced by mutations in fibrinogen Aα-chain gene (FGA).[2]
Epidemiology and Demographics
- Fibrinogen A a-chain amyloidosis (AFib) is emerging as the most common type of all hereditary renal amyloid diseases in the United Kingdom and Europe.
- A tertiary US amyloid reference center suggests fibrinogen A alpha-chain amyloidosis is the leading cause of hereditary renal amyloidosis associated with nephrotic syndrome in the United States.
Risk Factors
There are no specific risk factors associated with fibrinogen A alpha-chain amyloidosis.
Screening
There is insufficient evidence to recommend routine screening for Fibrinogen A a-chain amyloidosis.
Natural History, Complications, and Prognosis
Patients with fibrinogen amyloidosis usually develop chronic kidney disease, typically progressing to end-stage renal disease within 5 years of recognition of renal involvement.
Diagnosis
Diagnostic Study of Choice
- There is no single diagnostic study of choice for the diagnosis of fibrinogen amyloidosis.
- However, fibrinogen amyloidosis can be diagnosed based on the occurrence of proteinuric nephropathy, positive family history, identification of amyloid deposits in affected tissues by immunohistochemistry or mass spectrometry, and detection of an FGA amyloidogenic genetic variant.[6]
History and Symptoms
- Symptoms related to fibrinogen A a-chain amyloidosis (AFib) are aligned with the type of organ/organ system involved.
Physical Examination
- Physical examination of patients with fibrinogen A a-chain amyloidosis (AFib) depends on the type of the organ/organ system involved.
Laboratory Findings
- Laboratory findings of fibrinogen A a-chain amyloidosis (AFib) can include derangement in multiple serum markers.
- This derangement, when present, goes in line with the type of the organ/organ system involved.
Electrocardiogram
- There are no specific ECG findings associated with fibrinogen A a-chain amyloidosis (AFib).
- In case the heart is involved, findings can include:[7][8][9]
X-ray
There are no x-ray findings associated with fibrinogen amyloidosis.
Echocardiography or Ultrasound
- There are no specific echocardiographic or ultrasound findings associated with fibrinogen A a-chain amyloidosis (AFib).
- To read more in the case of involvement of the heart, click here.
CT scan
- There are no specific CT scan findings associated with fibrinogen A a-chain amyloidosis (AFib).
- To learn about the CT scan findings in the setting of an involved heart, click here.
MRI
- There are no specific MRI findings associated with fibrinogen A a-chain amyloidosis (AFib).
- For MRI findings in an involved heart click here.
Other Imaging Findings
- There are no other imaging findings associated with fibrinogen A a-chain amyloidosis (AFib).
Other Diagnostic Studies
- There are no other diagnostic studies associated with fibrinogen A a-chain amyloidosis (AFib).
Treatment
Medical Therapy
Fibrinogen production is exclusively hepatic. Isolated renal transplantation as a treatment for renal failure in fibrinogen amyloidosis is of limited value.[10]
Surgery
Surgery is not indicated in the management of fibrinogen A a-chain amyloidosis (AFib).
Primary Prevention
There are no established measures for the primary prevention of fibrinogen A a-chain amyloidosis (AFib).
Secondary Prevention
There are no established measures for the secondary prevention of fibrinogen A a-chain amyloidosis (AFib).
References
- ↑ Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R (1993). "Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain". Nat Genet. 3 (3): 252–5. doi:10.1038/ng0393-252. PMID 8097946.
- ↑ 2.0 2.1 Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R (1993). "Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain". Nat Genet. 3 (3): 252–5. doi:10.1038/ng0393-252. PMID 8097946.
- ↑ Rowczenio D, Stensland M, de Souza GA, Strøm EH, Gilbertson JA, Taylor G; et al. (2017). "Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein". Kidney Int Rep. 2 (3): 461–469. doi:10.1016/j.ekir.2016.11.005. PMC 5678610. PMID 29142973.
- ↑ Matsuda M, Sugo T (2001). "Hereditary disorders of fibrinogen". Ann N Y Acad Sci. 936: 65–88. doi:10.1111/j.1749-6632.2001.tb03494.x. PMID 11460526.
- ↑ Benson MD (2005). "Ostertag revisited: the inherited systemic amyloidoses without neuropathy". Amyloid. 12 (2): 75–87. doi:10.1080/13506120500106925. PMID 16011983.
- ↑ Gillmore JD, Lachmann HJ, Rowczenio D, Gilbertson JA, Zeng CH, Liu ZH; et al. (2009). "Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosis". J Am Soc Nephrol. 20 (2): 444–51. doi:10.1681/ASN.2008060614. PMC 2637055. PMID 19073821.
- ↑ Ridolfi RL, Bulkley BH, Hutchins GM (1977). "The conduction system in cardiac amyloidosis. Clinical and pathologic features of 23 patients". The American Journal of Medicine. 62 (5): 677–86. PMID 871125. Unknown parameter
|month=ignored (help) - ↑ Rahman JE, Helou EF, Gelzer-Bell R; et al. (2004). "Noninvasive diagnosis of biopsy-proven cardiac amyloidosis". Journal of the American College of Cardiology. 43 (3): 410–5. doi:10.1016/j.jacc.2003.08.043. PMID 15013123. Unknown parameter
|month=ignored (help) - ↑ Murtagh B, Hammill SC, Gertz MA, Kyle RA, Tajik AJ, Grogan M (2005). "Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement". The American Journal of Cardiology. 95 (4): 535–7. doi:10.1016/j.amjcard.2004.10.028. PMID 15695149. Unknown parameter
|month=ignored (help) - ↑ Mousson C, Heyd B, Justrabo E, Rebibou JM, Tanter Y, Miguet JP; et al. (2006). "Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen Aalpha-chain gene". Am J Transplant. 6 (3): 632–5. doi:10.1111/j.1600-6143.2005.01199.x. PMID 16468976.