Definition:

Familial Amyloid Polyneuropathy (FAP) is a rare hereditary disorder characterized by the buildup of abnormal proteins called amyloids, primarily affecting the peripheral nerves and various other organs within the body.

Subtypes:

FAP is classified into different subtypes depending on the specific protein involved:

  • Transthyretin (TTR) Amyloidosis: This is the most common form of FAP, caused by mutations in the transthyretin gene. It primarily affects the peripheral nerves and may lead to motor, sensory, and autonomic neuropathy.
  • Gelsolin Amyloidosis: This subtype is caused by mutations in the gelsolin gene and primarily affects the cranial and peripheral nerves.
  • Apolipoprotein A-I Amyloidosis: It is caused by mutations in the apolipoprotein A-I gene and primarily affects the kidneys, liver, and heart.
  • Lysosome-Associated Membrane Protein 2 (LAMP2) Amyloidosis: This rare subtype is caused by mutations in the LAMP2 gene and affects multiple organ systems, including the heart, kidneys, and liver.

Symptoms:

The symptoms of Familial Amyloid Polyneuropathy can vary depending on the subtype and organs affected. However, common symptoms include:

  • Sensory disturbances such as numbness, tingling, or pain
  • Muscle weakness and wasting
  • Autonomic dysfunction, leading to symptoms like orthostatic hypotension, gastrointestinal issues, and sexual dysfunction
  • Organ-specific symptoms depending on the subtype

Diagnosis:

Diagnosis of FAP involves a combination of clinical evaluation, family history analysis, genetic testing to identify the underlying mutations, and other tests such as nerve conduction studies, imaging, and biopsy of affected tissues.

Treatment:

Treatment for FAP aims to manage symptoms, slow disease progression, and improve the patient’s quality of life. This may involve the following:

  • Liver transplantation: In some cases of TTR amyloidosis, liver transplantation can replace the source of the mutant protein.
  • TTR stabilizers: Medications that stabilize the transthyretin protein can help slow its rate of amyloid production.
  • Symptomatic treatments: Addressing individual symptoms such as pain management, gastrointestinal support, physical therapy, and the use of assistive devices.
  • Novel therapies: Emerging treatments like gene silencing therapy and specific targeted medications are being investigated.

It is essential for patients with FAP to receive ongoing medical care, symptom management, and regular monitoring to optimize their health and well-being.