If you’re living with hereditary transthyretin (hATTR) amyloidosis, you may be curious about what it means for your family. The condition is an autosomal dominant disease, meaning there’s a 50 percent chance your children will inherit the gene and may develop the condition. Like many parents, you’re left waiting to see if your child will show signs of hATTR amyloidosis.

The age at which a person first starts showing symptoms of a disease is referred to as the age of onset. If you’ve done genetic testing and know you or your child is at risk of hATTR amyloidosis, you’re likely wondering when symptoms may begin.

This article will explain when symptoms of hATTR amyloidosis usually appear and what factors influence them. While genetics can’t be changed, several treatment options can help manage the disease.

What Is hATTR Amyloidosis, and How Is It Inherited?

Mutations (changes) in the transthyretin (TTR) gene cause hATTR amyloidosis. These changes interfere with how well the TTR protein can fold into the correct shape. A normal TTR protein is made of four subunits woven together, known as a tetramer.

In people with hATTR amyloidosis, mutations weaken the stability of forming TTR tetramers, causing them to break apart into monomers (separate strands). These protein strands form abnormal clumps called amyloid fibrils that get stuck in organs throughout the body. Known as amyloid deposits, the clumps begin interfering with how well organs work and eventually lead to symptoms.

Symptoms of hATTR amyloidosis can begin appearing in people as young as 20 years old and as old as 80. In the U.S., the median age of onset for hATTR amyloidosis is 68.

The genetic mutations responsible for causing hATTR amyloidosis are inherited from parents and are called autosomal dominant mutations. This means that to develop the disease, a person needs only one mutated copy of the TTR gene out of the two they inherit (one from each parent).

Who Develops hATTR Amyloidosis?

As mentioned, a parent with hATTR amyloidosis has a 50 percent chance of passing the mutated TTR gene to a child. However, having the mutation doesn’t automatically mean that the child will develop the disease. Still, many parents wonder if — or when — their child might start showing symptoms.

Researchers use the scientific term “penetrance” to refer to the number of people with a gene mutation who develop symptoms. Some mutations and populations have a higher penetrance than others.

Factors That Affect Age of Onset With hATTR Amyloidosis

Symptoms of hATTR amyloidosis can begin appearing in people as young as 20 years old and as old as 80. Studies show that in the U.S., the median age of onset for hATTR amyloidosis is 68. This means that half of people develop symptoms before 68, and half develop them after that age.

If you started developing symptoms at 60, your child is likely to start experiencing them around the same age.

The age of onset varies depending on family history, type of mutation, and types of symptoms.

Type of hATTR Amyloidosis Mutation

Doctors and researchers have discovered more than 120 mutations related to hATTR amyloidosis. Some of the most common gene mutations seem to be linked with certain ages of onset. Also, specific mutations are found in some countries more than others. In the U.S., doctors usually see the following mutations:

• Val122Ile (V122I)
• Val30Met (V30M)
• Thr60Ala (T60A)

The V122I mutation is found in around 3.2 percent of African Americans in the U.S., according to the Amyloidosis Research Consortium. Symptoms of hATTR amyloidosis in people with the V122I mutation tend to develop after age 60.

The V30M mutation is common in people from Japan, Sweden, and Portugal. According to the Amyloidosis Research Consortium, 80 percent of people from Portugal with the V30M mutation develop hATTR amyloidosis symptoms by age 50, and 91 percent have symptoms by 70.

By comparison, people from Sweden are much less likely to develop symptoms at an early age. Only 11 percent of people with the V30M mutation show signs of hATTR amyloidosis by age 50, and 52 percent experience symptoms by their 80th birthday.

The T60A mutation tends to affect people of Irish ethnicity. This mutation is associated with a later onset of symptoms — between ages 45 and 78 — and most commonly after 60.

Biological Sex

Males and females have an equal chance of inheriting mutated TTR genes from their parents, according to Rare Disease Advisor. This is because the TTR gene is located on chromosome 18, which isn’t a sex chromosome (X or Y). Doctors and researchers aren’t quite sure why, but males tend to develop hATTR amyloidosis more often and at a younger age than females.

Family History of hATTR Amyloidosis

The age of onset for hATTR amyloidosis can vary based on your family history of the disease. For example, if you developed symptoms at 60, your child is likely to start experiencing them around the same age. People with a family history of hATTR amyloidosis appear to be more likely to develop early-onset disease (under age 50).

Age of Onset Is Linked With Certain Symptoms

Did you know that the type of mutation and age of onset can affect which hATTR amyloidosis symptoms you experience?

You may have come across the terms “familial amyloid polyneuropathy” and “amyloid cardiomyopathy” as you’ve learned about this disease. Today, we understand that there are more types of amyloidosis, and they can be broken down by age of onset.

It can be scary to think about the potential of developing hATTR amyloidosis. Fortunately, several treatment options can slow disease progression and help you or a family member live a longer, healthier life.

Some studies have looked into the differences between early-onset and late-onset hATTR amyloidosis. Generally, people with early-onset disease develop symptoms before 50, while those with late-onset disease start experiencing symptoms after that age.

Neurological Symptoms

In a study from the journal Neurology and Therapy, nearly 1,400 people with V30M mutations were examined to find out the differences between early-onset and late-onset disease. Researchers found that people with late-onset disease typically had more motor neuropathy symptoms. This means they were more likely to experience weakness in their arms and legs, making movement more difficult.

On the other hand, those with early-onset hATTR amyloidosis tended to have more autonomic neuropathy. Your autonomic nervous system is responsible for regulating your body’s normal functions. The disease can damage these nerves, leading to problems with:

• Regulating blood pressure — Causes orthostatic hypotension (a drop in blood pressure after standing)
• Digestion — Causes gastrointestinal issues like nausea, vomiting, and constipation

Late-onset disease is also associated with peripheral neuropathy symptoms like numbness and tingling in the hands and feet. This group tends to develop carpal tunnel syndrome more often as well, leading to wrist problems.

Heart Symptoms

Cardiovascular problems were also more common in people with late-onset hATTR amyloidosis. People with heart problems from this disease can experience shortness of breath, arrhythmias (abnormal heart rhythms), and dizziness.

Eventually, the buildup of amyloid fibrils in the heart — known as cardiac amyloidosis — can lead to heart failure.

Discuss Treatment Options With Your Doctor

It can be scary to think about the potential of developing hATTR amyloidosis. Fortunately, several treatment options can slow disease progression and help you or a family member live a longer, healthier life. Treatments for hATTR include TTR stabilizers and gene-silencing therapies. In some cases, a healthcare provider may opt to manage hATTR by prescribing a drug “off-label” — using it for a condition other than what the FDA officially approved.

If you’re interested in learning more about the available hATTR amyloidosis treatments and when you or a family member should start treatment, talk to your doctor. Your healthcare team can help you by offering personalized information, discussing potential benefits and risks, and guiding you in making informed decisions about managing your condition. They’re dedicated to supporting you on your journey and ensuring the best possible care tailored to your needs.

Talk With Others Who Understand

MyAmyloidosisTeam is the social media network for people with amyloidosis and their loved ones. Members come together to ask questions, give advice, and share their experiences with others who understand life with amyloidosis.

Do you still have questions about the age of onset with hereditary transthyretin amyloidosis? Leave a comment below, or start a conversation by posting on your Activities page.