Summary about Disease
Familial Amyloid Polyneuropathy (FAP), also known as transthyretin amyloidosis (ATTR amyloidosis), is a rare, progressive, inherited disorder characterized by the buildup of abnormal amyloid protein, primarily transthyretin (TTR), in various tissues and organs throughout the body. This amyloid deposition disrupts the normal function of these tissues and organs, leading to a range of symptoms. The most commonly affected areas include the peripheral nerves, heart, kidneys, and eyes.
Symptoms
Symptoms of FAP vary greatly from person to person but may include:
Peripheral Neuropathy: Tingling, numbness, pain, and weakness, typically starting in the feet and legs and progressing upwards.
Autonomic Dysfunction: Problems with blood pressure regulation (orthostatic hypotension), heart rate abnormalities, bowel irregularities (constipation or diarrhea), urinary dysfunction, and erectile dysfunction.
Cardiomyopathy: Heart muscle thickening and stiffening, leading to heart failure.
Kidney Involvement: Proteinuria (protein in the urine) and eventual kidney failure.
Eye Problems: Vitreous opacities (clouding of the gel-like substance in the eye), glaucoma, and dry eyes.
Carpal Tunnel Syndrome: Pain, numbness, and tingling in the hand and fingers.
Weight Loss: Unexplained weight loss despite adequate food intake.
Causes
FAP is caused by a mutation in the TTR gene, which provides instructions for making transthyretin protein. Mutated TTR protein is unstable and prone to misfolding and clumping together to form amyloid fibrils. These fibrils deposit in various tissues and organs, causing damage. The disease is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is sufficient to cause the disease.
Medicine Used
TTR Stabilizers: These medications, such as tafamidis and diflunisal, work by stabilizing the TTR protein and preventing it from misfolding and forming amyloid fibrils.
TTR Gene Silencers: These therapies, such as patisiran (an siRNA) and inotersen (an antisense oligonucleotide), reduce the production of TTR protein in the liver.
Liver Transplant: Replacing the liver can eliminate the source of the mutated TTR protein. It is often performed early in the disease course.
Supportive Therapies: Medications to manage specific symptoms, such as pain relievers, anti-arrhythmics, and medications for heart failure.
Is Communicable
No, Familial Amyloid Polyneuropathy is not communicable. It is a genetic disorder caused by a mutation in the TTR gene and is inherited from parent to child. It cannot be spread through contact with an affected individual.
Precautions
There are no specific precautions to prevent getting FAP as it is a genetic condition. However, for individuals with a family history of FAP, genetic counseling and testing can help determine their risk of inheriting the gene mutation and developing the disease. Early diagnosis and treatment are crucial for managing the symptoms and slowing the progression of the disease.
How long does an outbreak last?
FAP is not characterized by outbreaks. It is a chronic, progressive disease. The symptoms gradually worsen over time. The rate of progression varies depending on the specific mutation, the individual's overall health, and the treatment received.
How is it diagnosed?
Diagnosis of FAP typically involves:
Clinical Evaluation: Review of the patient's symptoms, medical history, and family history.
Neurological Examination: Assessment of nerve function, muscle strength, and reflexes.
Genetic Testing: Analysis of the TTR gene to identify mutations.
Biopsy: Tissue sample (e.g., nerve, fat, heart) to confirm the presence of amyloid deposits. Congo red staining is used to identify amyloid.
Echocardiogram: To assess heart function.
Electromyography (EMG) and Nerve Conduction Studies: To evaluate nerve damage.
Blood and Urine Tests: To assess kidney function and detect the presence of TTR protein.
Nuclear Imaging: Scans with tracers that bind to TTR amyloid, like PYP scans.
Timeline of Symptoms
The timeline of symptoms varies greatly depending on the specific mutation and individual factors. However, a general progression might look like this:
Early Stage: Numbness, tingling, and pain in the feet and legs, often starting in the toes and gradually progressing upwards. Autonomic dysfunction symptoms may also appear.
Intermediate Stage: Weakness in the legs and arms, difficulty walking, worsening autonomic dysfunction, and development of cardiac or kidney problems.
Late Stage: Severe muscle weakness, loss of mobility, significant organ damage (heart failure, kidney failure), and dependence on assistive devices or care.
Important Considerations
Genetic Counseling: Essential for individuals with a family history of FAP to understand the inheritance pattern and risk of passing the gene mutation to their children.
Early Diagnosis and Treatment: Crucial for slowing the progression of the disease and improving the quality of life.
Multidisciplinary Care: Management of FAP requires a team of specialists, including neurologists, cardiologists, nephrologists, ophthalmologists, and genetic counselors.
Disease Monitoring: Regular follow-up appointments and testing are necessary to monitor disease progression and adjust treatment as needed.
Clinical Trials: Patients may consider participating in clinical trials to access new therapies and contribute to research on FAP.
Psychological Support: Dealing with a chronic and progressive disease like FAP can be emotionally challenging. Access to psychological support and counseling can be beneficial.