Amyloidosis, familial

Familial Amyloidosis
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Peripheral neuropathy, Cardiomyopathy, Nephropathy
Complications	Heart failure, Kidney failure
Onset	Typically adulthood
Duration	Chronic
Types	N/A
Causes	Genetic mutations
Risks	Family history
Diagnosis	Genetic testing, Biopsy
Differential diagnosis	N/A
Prevention	N/A
Treatment	Liver transplantation, Tafamidis, Patisiran
Medication	N/A
Prognosis	Variable
Frequency	Rare
Deaths	N/A

Familial Amyloidosis is a group of inherited disorders characterized by the abnormal deposition of amyloid proteins in various tissues and organs. This condition is caused by mutations in specific genes that lead to the production of misfolded proteins, which aggregate and form amyloid fibrils.

Pathophysiology

Familial amyloidosis is primarily caused by mutations in the TTR gene (transthyretin), although other genes such as APOA1, APOA2, and Gelsolin can also be involved. The mutated proteins misfold and aggregate into insoluble fibrils that deposit in tissues, disrupting normal function. The most common form, transthyretin amyloidosis, affects the peripheral nervous system, heart, and kidneys.

Clinical Manifestations

The clinical presentation of familial amyloidosis varies depending on the organs involved and the specific genetic mutation. Common symptoms include:

• Peripheral neuropathy: Patients may experience numbness, tingling, and pain in the extremities.
• Cardiomyopathy: Amyloid deposits in the heart can lead to restrictive cardiomyopathy, resulting in heart failure.
• Nephropathy: Kidney involvement can cause proteinuria and progressive renal failure.
• Gastrointestinal symptoms: Some patients may experience diarrhea, constipation, or weight loss.
• Ocular involvement: Amyloid deposits can affect the eyes, leading to vision problems.

Diagnosis

The diagnosis of familial amyloidosis involves a combination of clinical evaluation, family history, and specialized tests:

• Genetic testing: Identifies specific mutations in genes associated with amyloidosis.
• Biopsy: Tissue samples from affected organs can be stained with Congo red dye, which shows apple-green birefringence under polarized light, confirming amyloid deposits.
• Imaging studies: Echocardiography and MRI can assess organ involvement, particularly in the heart.

Treatment

Treatment strategies for familial amyloidosis focus on managing symptoms and slowing disease progression:

• Liver transplantation: Effective for transthyretin amyloidosis, as the liver is the primary source of mutant transthyretin.
• Tafamidis: A stabilizer of transthyretin, it slows the progression of neuropathy and cardiomyopathy.
• Patisiran and Inotersen: RNA interference therapies that reduce the production of transthyretin.
• Supportive care: Includes management of heart failure, pain control, and nutritional support.

Prognosis

The prognosis of familial amyloidosis varies widely depending on the type of mutation, organs involved, and the timeliness of treatment. Early diagnosis and intervention can improve outcomes, but the disease often leads to significant morbidity and mortality.

Epidemiology

Familial amyloidosis is a rare condition, with varying prevalence depending on the specific mutation and geographic region. Certain mutations, such as the Val30Met in transthyretin, are more common in specific populations, such as those in Portugal, Sweden, and Japan.

See also

• Amyloidosis
• Transthyretin
• Genetic disorders