Familial amyloidosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.
Overview
Historical Perspective
In 1639, Nicolaus Fontanus autopsied a young man who had ascites, jaundice, liver abscess, and splenomegaly and his report has been the first description of amyloidosis. There is no significant data regarding the historical perspective of amyloidosis throughout the 18th century. Rudolph Virchow and Weber are the prominent figures with substantial work on amyloidosis during the 19th century. In 1922, Bennhold introduced Congo Red staining of amyloid that remains the gold standard for diagnosis.
Classification
Familiar amyloidosis may be classified according to the type of mutant protein into 7 subtypes: Transthyretin amyloidosis (TTR), apolipoprotein AI, cystatin C, lysozyme, fibrinogen A alpha-chain, gelsolin, and apolipoprotein AII.
Pathophysiology
It is understood that amyloidosis is the result of deposition of Amyloid. Amyloid is an abnormal insoluble extracellular protein which may cause organ dysfunction and a wide variety of clinical syndromes. Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure. Genetic mutations in different genes may lead to misfolding protein product. Genes involved in the pathogenesis of familial amyloidosis include transthyretin, apolipoprotein AI, apolipoprotein AII, Lysozyme, gelsolin, fibrinogen Aa-chain, and cystatin C.
Causes
Hereditary amyloidosis can be caused by genetic mutations in different genes.
Differentiating Familial amyloidosis from Other Diseases
Familial amyloidosis may affect any organ in the body but the most commonly affected organs are the heart, kidneys and nerves. Involvement of these organ systems may give rise to organ failure, therefore early diagnosis is imperative for optimal treatment. Organ specific amyloidosis should be differentiated from other diseases that mimic amyloidosis and may present as organ dysfunction, specifically, nephrotic syndrome leading to renal failure, cardiac failure and polyneuropathy.
Epidemiology and Demographics
The incidence of amyloidosis is approximately 1.2 per 100,000 individuals per year worldwide. The mortality rate of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries. In familial amyloidosis, the mean age of presentation for TTR amyloidosis is after 50 years old and for other types is mostly third to forth decade of life. Men are more commonly affected by amyloidosis than women.
Risk Factors
Common risk factors in the development of familial amyloidosis include older age, male gender, african american race, and positive family history.
Screening
There is insufficient evidence to recommend routine screening for familial amyloidosis.
Natural History, Complications, and Prognosis
The symptoms of familial amyloidosis usually develop after 50 years of age in TTR amyloidosis and late adulthood for other subtypes. In patients with familial amyloidosis, the most frequent complications include heart failure, nephrotic syndrome, hepatomegaly, and peripheral neuropathy. Prognosis is generally poor. The prognosis varies based on the type of organ involvement with amyloid heart disease have the worst prognosis. TTR amyloidosis patients have 60 months survival from presentation with heart failure symptoms.
Diagnosis
Diagnostic Study of Choice
The diagnostic study of choice in amyloidosis is tissue biopsy of the affected organ. Congo Red staining will show apple green birefringence of the tissue sample under polarized light.
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
CT scan can be done to assess for amyloid deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. However, MRI is more sensitive than CT in the diagnosis of amyloidosis.
MRI
MRI is commonly done to assess for amyloid deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. However, MRI is more sensitive than CT in the diagnosis of amyloidosis. A cardiac MRI is used when an echocardiogram fails to differentiate amyloidosis from hypertrophic cardiomyopathy.
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Organ-specific transplant may need to be done, depending on the organ involved. However, surgery is not commonly done in patients with amyloidosis, since it is usually a systemic disease that requires treatment of the underlying cause.
Primary Prevention
There is no role for primary prevention in familial amyloidosis.
Secondary Prevention
There is no role for secondary prevention in familial amyloidosis.