Portuguese type amyloidosis

Portuguese Type Amyloidosis

Portuguese Type Amyloidosis, also known as Familial Amyloid Polyneuropathy (FAP), is a hereditary form of amyloidosis that primarily affects the peripheral nervous system. It is caused by mutations in the transthyretin (TTR) gene, leading to the deposition of amyloid fibrils in various tissues and organs. This condition is particularly prevalent in certain regions of Portugal, hence its name.

Pathophysiology

The disease is caused by a mutation in the transthyretin (TTR) gene, which is located on chromosome 18. Transthyretin is a protein that transports thyroxine and retinol-binding protein bound to retinol. In Portuguese Type Amyloidosis, the most common mutation is the substitution of methionine for valine at position 30 (Val30Met). This mutation causes the TTR protein to misfold and aggregate into amyloid fibrils, which deposit in tissues and cause damage.

Clinical Presentation

Patients with Portuguese Type Amyloidosis typically present with symptoms in their third or fourth decade of life. The disease primarily affects the peripheral nerves, leading to a progressive polyneuropathy. Symptoms include:

- Sensory loss: Patients often experience numbness, tingling, and pain in the extremities. - Motor weakness: Muscle weakness and atrophy can occur, leading to difficulties in movement. - Autonomic dysfunction: This can manifest as gastrointestinal disturbances, orthostatic hypotension, and urinary incontinence.

In addition to neuropathy, amyloid deposits can affect the heart, kidneys, and eyes, leading to cardiomyopathy, renal impairment, and vitreous opacities, respectively.

Diagnosis

The diagnosis of Portuguese Type Amyloidosis is based on clinical evaluation, family history, and genetic testing. A biopsy of affected tissue, such as nerve or abdominal fat, can demonstrate amyloid deposits. Genetic testing can confirm the presence of the TTR mutation.

Treatment

Treatment options for Portuguese Type Amyloidosis include:

- Liver transplantation: Since the liver is the primary source of mutant TTR production, liver transplantation can halt the progression of the disease. - Tafamidis and diflunisal: These are TTR stabilizers that prevent the misfolding of the protein. - Patisiran and inotersen: These are RNA interference therapies that reduce the production of TTR.

Prognosis

The prognosis of Portuguese Type Amyloidosis varies depending on the age of onset and the organs involved. Early diagnosis and treatment can improve outcomes and quality of life.

Epidemiology

Portuguese Type Amyloidosis is most prevalent in Portugal, particularly in the Póvoa de Varzim and Vila do Conde regions. It is also found in other countries, including Sweden, Japan, and Brazil, due to migration and genetic factors.

Also see

- Amyloidosis - Transthyretin - Peripheral neuropathy - Genetic disorders