Hereditary transthyretin amyloidosis (ATTRv)

What happens in this disease?

A change in the TTR gene alters the structure of a protein called transthyretin. The faulty protein clumps together and forms deposits called amyloid. These build up mostly in the nerves and the heart. The eyes, kidneys and digestive system can also be affected.

Which symptoms can occur?

The age at onset varies widely; it is usually between 20 and 70. Symptoms progress slowly.

• Numbness, tingling and loss of feeling starting in the feet (common)
• Weakness in the arms and legs
• Bouts of diarrhea and constipation, nausea
• A drop in blood pressure on standing up
• Bladder and sexual function problems
• Heart rhythm problems and heart failure
• Carpal tunnel syndrome, which causes numbness in the hand
• Blurred vision or raised eye pressure (sometimes)

How is it diagnosed?

The diagnosis is made from the symptoms, examination and tests. Amyloid deposits are shown with a tissue sample or with heart imaging. A genetic test finds the change in the TTR gene. Family members can also be tested early.

Treatment and care

There are approved treatments specific to the disease. These are gene-silencing treatments that reduce the production of the faulty protein, and treatments that keep the protein stable. In selected people, a liver transplant may be considered. Pain, heart, eye and digestive problems are treated separately. Physiotherapy and yearly check-ups are important. The doctor who follows the disease decides which treatment is suitable.

For the family: inheritance and genetic counselling

The disease is passed on through dominant inheritance. For each child of a parent with the gene change, the chance of passing it on is 1 in 2. But not everyone with the gene change develops the disease. Relatives of patients can have a genetic test. This way, treatment can be started early. Genetic counselling is recommended.