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Understanding Hereditary Transthyretin Amyloidosis (hATTR) With Polyneuropathy

Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy is a rare genetic disorder that affects multiple organs and nerves in the body. This condition is caused by a mutation in the TTR gene, which leads to the production of abnormal transthyretin proteins that form amyloid deposits in various tissues. These deposits can cause serious complications and even death if left untreated.

Causes and Risk Factors

hATTR is an inherited condition passed down through families. If one or both of your parents have the mutated TTR gene, you may inherit the disorder. While the exact prevalence is unknown, hATTR is more common in certain regions, such as parts of Brazil, Japan, Portugal, and Sweden. In the United States, it is estimated that around 6,400 people have hATTR, with a higher incidence among Americans of European, Black, and Irish descent.

Symptoms

The symptoms of hATTR can vary depending on the organs and nerves affected by amyloid deposits. Some common symptoms include:

  • Numbness, tingling, and swelling in the hands and feet

  • Digestive problems, such as diarrhea, constipation, and early satiety

  • Urinary tract issues and sexual dysfunction

  • Fatigue and weakness

  • Eye problems, including cloudiness, dry eyes, and increased pressure (glaucoma)

  • Heart complications, such as enlargement and irregular heartbeats

Diagnosis

Diagnosing hATTR can be challenging due to its similarity to other conditions. If you have a family history of the disorder, your doctor may recommend genetic testing to check for the mutated TTR gene. Other diagnostic tests may include:

  • Blood and urine tests to check for excess protein

  • Tissue biopsy to detect amyloid deposits

  • Bone scans (scintigraphy) to identify amyloid deposits in the heart

  • Genetic testing to differentiate between hereditary and non-hereditary forms of ATTR amyloidosis

Treatment Options

Treatment for hATTR focuses on managing symptoms and slowing the progression of the disease. Some options include:

  • Gene silencer drugs, such as inotersen, patisiran, and vutrisiran, which stop the production of TTR protein

  • Liver transplantation, which may slow the disease progression but carries risks and requires lifelong immunosuppressive therapy

  • Gene stabilizer drugs, such as tafamidis, diflunisal, and doxycycline, which prevent TTR proteins from misfolding and forming amyloid deposits

  • Symptom management with medications for fluid retention, digestive issues, and other complications

Researchers are also exploring innovative treatments, such as antibodies to remove amyloid deposits and new drugs to suppress or stabilize the TTR gene.

Disease Progression and Complications

hATTR with polyneuropathy is a progressive disorder that advances through several stages:

  • Stage 0: No symptoms, but genetic testing reveals the TTR mutation

  • Stage I: Mild sensory, motor, and autonomic neuropathy in the lower limbs

  • Stage II: Moderate involvement of upper and lower limbs, as well as the trunk, with difficulty walking

  • Stage III: Severe motor, sensory, and autonomic involvement of all limbs, often requiring a wheelchair

Complications of hATTR can include peripheral nervous system issues, autonomic dysfunction affecting internal organs, irregular heartbeat, heart failure, kidney failure, eye problems, and pain.

Coping With hATTR

Living with hATTR can be challenging, but a multidisciplinary care team can help manage the various aspects of the disorder. This team may include a genetic counselor, neurologist, cardiologist, nephrologist, ophthalmologist, and physical therapist. It is essential to maintain open communication with your healthcare providers and seek support from family, friends, and patient advocacy groups.

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