Transthyretin-related hereditary amyloidosis is an autosomal dominant disorder with variable penetrance. It is caused by mutations of the TTR gene.
Three types of ATTR amyloidosis can be distinguished based on dominating symptoms.
FAP, neuropathic amyloidosis, is dominated by peripheral neuropathy.
In FAC, cardiac amyloidosis, heart failure is the most obvious clinical finding.
A third type, senile systemic amyloidosis, which is also characterized by transthyretin deposits is not related to TTR mutations and therefore not hereditary.
Organs involved in transthyretin-related hereditary amyloidosis include heart and peripheral nerves. More rarely, gastrointestinal and renal involvement is observed.
The affected heart shows enlargement and progressive failure. If cardiac involvement dominates the clinical picture we call the disease familial amyloid cardiomyopathy (FAC).
The peripheral polyneuropathy predominantly affects autonomous and somatic fibers. This disease is rapidly progressive. It is accompanied by carpal tunnel syndrome and muscle loss. If the involvement of the peripheral nervous system dominates the clinical picture we call the disorder familial amyloid polyneuropathy (FAP).
Some of the gastrointestinal sumptoms such as diarrhea and obstipation are also related to peripheral autonomous neuropathy. Often the symptoms resemble food intolerance.
Renal symptoms include proteinuria and renal insufficiency. Both are rather mild and therefore often ignored.
Since 1991 therapy includes liver transplatation which eleminates the main source of misfolded transthyretin. With significant cardiomyopathy a combined heart and liver transplantation can be considered. Since 2011 a drug to prevent misfolded transthyretin is approved for the treatment of FAP and the approval for FAC is on its way.
Polyneuropathy | |
Polyneuropathy preferentially autonomous and somatic is the dominating symptom of FAP. |
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Cardiomyopathy | |
Cardiomyopathy in FAC is predominantly characterized by cardiomegaly and reduced physical capacity. |
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Muscle atrophy | |
Muscle loss in FAP is the result of polyneuropathy. It presents with gait abnormality. |
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Diarrhea | |
Diarrhea and obstipation can alternate. They are the result of autonomous polyneuropathy. |
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Proteinuria | |
Proteinuria might be only mild but signals renal involvement. |
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Renal insufficiency | |
Though renal insufficiency may develop due to renal involvement, this condition will rarely dominate the clinical picture. |
Hereditary amyloidosis | ||||
ATTR amyloidosis | ||||
TTR | ||||
Amyloidosis, cerebroarterial | ||||
Cryopyrin-associated periodic syndrome | ||||
Familial Mediterranean fever | ||||
Finnish type Amyloidosis | ||||
Hereditary renal amyloidosis | ||||
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