What are the symptoms of transthyretin familial amyloid polyneuropathy?

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, progressive, and often fatal genetic disorder caused by mutations in the transthyretin gene. The condition is characterized by the buildup of abnormal deposits of protein called amyloid fibrils in various tissues and organs, including nerves, heart, and gastrointestinal tract. Symptoms of TTR-FAP can vary depending on the organs affected, but common symptoms may include:

1. Peripheral neuropathy: TTR-FAP often initially affects the peripheral nerves, leading to symptoms such as numbness, tingling, burning pain, or weakness in the hands and feet. This neuropathy typically progresses and can lead to difficulties with balance and coordination.
2. Autonomic dysfunction: TTR-FAP can also affect the autonomic nervous system, leading to symptoms such as orthostatic hypotension (a drop in blood pressure upon standing), gastrointestinal disturbances (such as diarrhea, constipation, or nausea), urinary problems (such as incontinence in both men and women, or difficulty urinating), and sexual dysfunction in both men and women.
3. Cardiac involvement: TTR-FAP can affect the heart, leading to symptoms such as palpitations, shortness of breath, fatigue, and eventually heart failure.
4. Other symptoms: Depending on the organs affected, TTR-FAP can also cause symptoms such as weight loss, fatigue, swelling of the limbs (edema), and difficulty swallowing.

The age of onset and rate of progression of TTR-FAP can vary widely depending on the specific mutation involved. The condition is typically progressive and can lead to significant disability and a shortened lifespan. Early diagnosis and management are important in order to slow the progression of the disease and manage symptoms. Treatment options may include medications to stabilize or reduce the production of abnormal transthyretin protein, as well as supportive care to manage symptoms and complications.

What are the causes of transthyretin familial amyloid polyneuropathy?

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is caused by mutations in the transthyretin (TTR) gene. The TTR gene provides instructions for making a protein called transthyretin, which is produced mainly in the liver and helps transport thyroid hormone and vitamin A in the bloodstream.

Mutations in the TTR gene can cause the transthyretin protein to become unstable and misfold. These misfolded proteins can then accumulate as amyloid fibrils in various tissues and organs, including nerves, heart, and gastrointestinal tract. The buildup of amyloid fibrils disrupts normal tissue structure and function, leading to the symptoms of TTR-FAP.

TTR-FAP is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. However, not all individuals with a TTR gene mutation will develop TTR-FAP, and the age of onset and severity of the condition can vary widely even among individuals with the same mutation.

Certain mutations in the TTR gene are more commonly associated with TTR-FAP, and the condition tends to run in families. However, new mutations can also occur spontaneously in individuals with no family history of the condition.

The exact mechanisms by which the buildup of amyloid fibrils leads to the symptoms of TTR-FAP are not fully understood, and research into the underlying biology of the condition is ongoing.

What is the treatment for transthyretin familial amyloid polyneuropathy?

The treatment for transthyretin familial amyloid polyneuropathy (TTR-FAP) aims to stabilize or reduce the production of abnormal transthyretin protein, manage symptoms, and improve quality of life. Treatment options may include:

1. Tafamidis: Tafamidis is a medication that can stabilize the transthyretin protein, preventing it from forming amyloid fibrils. Tafamidis has been shown to slow the progression of neurological impairment in people with early-stage TTR-FAP.
2. Liver transplantation: Liver transplantation can be considered in some cases of TTR-FAP. Since the liver is the primary site of transthyretin production, replacing the liver with a healthy donor liver can reduce the production of abnormal transthyretin protein. However, this treatment option is not suitable for all patients and carries risks.
3. Orthotopic liver transplantation (OLT): Orthotopic liver transplantation involves removing the diseased liver and replacing it with a healthy donor liver. OLT can halt the progression of TTR-FAP by replacing the liver’s source of mutated transthyretin with normal transthyretin.
4. Supportive care: Supportive care is an important part of managing TTR-FAP and may include physical therapy, occupational therapy, and assistive devices to help manage symptoms and improve quality of life.
5. Symptomatic treatments: Medications may be prescribed to manage specific symptoms of TTR-FAP, such as pain, gastrointestinal symptoms, and autonomic dysfunction.
6. Monitoring and management of complications: Regular monitoring and management of complications, such as cardiac involvement, are important in the care of individuals with TTR-FAP.

The choice of treatment depends on several factors, including the specific mutation causing TTR-FAP, the stage of the disease, and the individual’s overall health and preferences. Treatment decisions should be made in consultation with a healthcare provider who is familiar with the management of TTR-FAP.