Hereditary Transthyretin-Mediated Amyloidosis

Hereditary Transthyretin-Mediated Amyloidosis (hATTR) is a rare, progressive, and life-threatening genetic disorder. It occurs when a mutation in the TTR gene causes the liver to produce abnormal, "misfolded" transthyretin proteins.

These misfolded proteins clump together to form amyloid fibrils, which deposit in various organs and tissues throughout the body—most commonly the nerves, heart, and digestive system. Because it is hereditary, it can be passed down through families, though the age of onset and severity of symptoms vary significantly.

Key Symptoms and Manifestations

The symptoms of hATTR can be elusive because they often mimic other, more common conditions. Doctors typically categorize the symptoms into two main "tracks," though many patients experience a overlap of both.

1. Polyneuropathy (Nerve Damage)

• Sensory Loss: Tingling, numbness, or "burning" sensations in the hands and feet.

• Motor Weakness: Difficulty walking or loss of fine motor skills in the hands.

• Autonomic Dysfunction: Issues with involuntary functions, such as extreme dizziness when standing (orthostatic hypotension), bladder issues, or sexual dysfunction.

2. Cardiomyopathy (Heart Impact)

• Shortness of breath (dyspnea), even during rest.

• Persistent cough or wheezing.

• Swelling in the legs, ankles, and feet (edema).

• Arrhythmias or palpitations.

3. Gastrointestinal Issues

• Severe bouts of diarrhea alternating with constipation.

• Unintentional weight loss and nausea.

• Early satiety (feeling full after just a few bites).

The Genetics Behind the Condition

The disease is caused by mutations in the TTR gene, which provides instructions for making the transthyretin protein. Under normal circumstances, this protein transports Vitamin A and thyroid hormone in the blood.

Note: hATTR follows an autosomal dominant inheritance pattern. This means a person only needs one copy of the mutated gene from one parent to be at risk of developing the disease. However, not everyone with the mutation will necessarily develop symptoms (a concept known as "incomplete penetrance").

Diagnosis and Testing

Early diagnosis is critical because hATTR is a progressive disease. The sooner treatment begins, the better the chances of slowing organ damage.