Some forms of amyloidosis are hereditary, but most are not. Amyloidosis is actually a group of diseases, not a single condition, and they differ significantly in their causes. The most common hereditary form is caused by mutations in a gene called TTR, while the most frequently diagnosed types overall are acquired, meaning they develop on their own without being passed down through families.
Which Types Are Hereditary
The hereditary form most people encounter is called hereditary transthyretin amyloidosis (often abbreviated hATTR or ATTRv). It’s caused by a mutation in the TTR gene, which provides instructions for making a protein called transthyretin. When the gene is mutated, the protein misfolds and clumps into abnormal deposits called amyloid fibrils that accumulate in organs like the heart and nerves. An estimated 10,000 to 40,000 people worldwide have this form.
There are also rarer hereditary forms caused by mutations in other genes, including those that produce apolipoprotein A-I, apolipoprotein A-II, gelsolin, fibrinogen, and lysozyme. These are uncommon enough that hereditary transthyretin amyloidosis accounts for the vast majority of inherited cases.
One indirect hereditary connection worth knowing about: a condition called familial Mediterranean fever (FMF) is a genetic inflammatory disease passed down in an autosomal recessive pattern. Up to 8.6% of people with FMF develop a type of amyloidosis called AA amyloidosis as a complication. The amyloidosis itself isn’t directly inherited in these cases, but the underlying genetic condition that triggers it is.
Which Types Are Not Hereditary
The most common forms of amyloidosis are acquired, meaning they arise from other processes in the body rather than inherited gene mutations.
- AL amyloidosis (primary): This is the most frequently diagnosed systemic form. It develops when abnormal plasma cells in the bone marrow produce misfolded antibody fragments that deposit as amyloid. It is not inherited.
- AA amyloidosis (secondary): Caused by chronic infections or long-standing inflammatory diseases like rheumatoid arthritis. The body’s persistent inflammation drives overproduction of an inflammatory protein that eventually deposits as amyloid.
- Wild-type ATTR amyloidosis (ATTRwt): This one can be confusing because it involves the same transthyretin protein as the hereditary form, but there’s no gene mutation involved. The normal, unmutated protein gradually misfolds with aging, typically causing heart problems in older men. It was formerly called “senile systemic amyloidosis.” This form is more common than the hereditary version, affecting an estimated 200,000 to 300,000 people globally.
How Hereditary Amyloidosis Is Passed Down
Hereditary transthyretin amyloidosis follows an autosomal dominant inheritance pattern. That means only one copy of the mutated gene is needed to cause disease. If one of your parents carries the mutation, you have a 50% chance of inheriting it.
More than 100 different mutations in the TTR gene have been identified. The most common worldwide is a variant called Val50Met (previously known as Val30Met), which accounts for roughly 48% of symptomatic cases globally. The second most common is Val142Ile, found in about 6% of cases. There are significant regional differences: Val50Met dominates in Europe, Asia, and South America, while wild-type (non-hereditary) ATTR is the most commonly diagnosed form in North America.
Carrying the mutation doesn’t guarantee you’ll develop symptoms. The disease has variable penetrance, meaning some carriers develop severe symptoms while others may remain symptom-free for decades or even their entire lives. The age symptoms appear also varies by mutation and family history.
Genetic Testing and Family Screening
Genetic testing for hereditary transthyretin amyloidosis is straightforward. It requires only a blood sample, saliva sample, or cheek swab and looks for mutations in the TTR gene. If someone in your family has been diagnosed with the hereditary form, the American Heart Association recommends that all first-degree relatives (parents, siblings, and children) consider genetic testing and counseling for that specific mutation.
For family members who test positive but don’t yet have symptoms, annual monitoring is the standard approach. This typically includes neurological evaluations (nerve conduction studies, sensory testing, checks for autonomic problems like blood pressure changes on standing), cardiac screening with echocardiography and heart function blood markers, along with eye and kidney assessments. As a carrier approaches the age when symptoms appeared in other family members, monitoring may become more frequent and more detailed.
Psychological support is also built into the process at many specialized centers, with follow-up visits to a psychologist or counselor in the weeks and months after receiving a positive genetic result.
Treatment Options for Hereditary Forms
Hereditary transthyretin amyloidosis has seen a dramatic shift in treatment over the past several years. Two main approaches are now available.
The first strategy is protein stabilizers, which work by binding to the transthyretin protein and preventing it from misfolding. Acoramidis is among the newer stabilizers showing strong results in clinical trials. The second, more targeted strategy uses gene-silencing therapies that reduce the body’s production of the problematic protein altogether. These drugs work in the liver, where most transthyretin is made, and shut down production of both the mutated and normal versions of the protein. Two recently approved gene silencers, vutrisiran and eplontersen, are administered as subcutaneous injections and are designed to be taken up specifically by liver cells. Vutrisiran works by using small RNA molecules to destroy the genetic instructions for making transthyretin before the protein is built. Eplontersen uses a slightly different mechanism to trigger the same result.
These treatments are most effective when started early, which is one of the strongest practical reasons for genetic testing and regular monitoring in families with a known mutation. Catching the disease before significant organ damage accumulates changes the trajectory considerably.