There are two main types (or phenotypes) of transthyretin amyloidosis (ATTR): transthyretin amyloid cardiomyopathy (ATTR-CM) and transthyretin amyloid polyneuropathy (ATTR-PN). But some patients straddle both categories, with both their heart and nervous system affected. These patients have a mixed ATTR phenotype.
What is a phenotype in ATTR?
A phenotype refers to how the disease affects the body, including which organs are affected and the associated symptoms.
In ATTR, the cardiac phenotype (ATTR-CM) affects the heart. Misfolded TTR proteins build up in the heart, causing the heart muscle to thicken and stiffen and restricting the ability of the heart to pump blood around the body. This leads to symptoms similar to those of heart failure, such as shortness of breath, wheezing, coughing, fatigue, palpitations, irregular heartbeat, brain fog and swelling in the abdomen, legs and feet.
Read more about ATTR-CM signs and symptoms
The neurologic phenotype (ATTR-PN) affects the nervous system. Instead of TTR proteins building up in the heart, they build up in the peripheral nerves, leading to nerve damage. Resulting symptoms can include muscle weakness, burning, numbness or tingling in the feet and hands, loss of coordination, dizziness when standing up, digestive problems, bladder dysfunction and erectile dysfunction.
What is a mixed ATTR phenotype?
A mixed ATTR phenotype means amyloid proteins build up in both the heart and the nerves, creating both cardiac and neurologic symptoms. Patients with a mixed phenotype often face a substantial symptom burden that is a challenge to manage in daily life.
A mixed phenotype often means a longer time to diagnosis, as overlapping and non-specific symptoms can make it harder for doctors to reach the correct diagnosis. Mixed ATTR is also less common than ATTR-CM and ATTR-PN, making it even harder for doctors to recognize and diagnose.
In some cases, a mixed ATTR phenotype can be the result of either ATTR-CM or ATTR-PN progressing and evolving to include a wider range of symptoms.
How is a mixed ATTR phenotype managed?
Patients with a mixed ATTR phenotype need a multidisciplinary medical approach. A cardiologist and a neurologist will work together to coordinate treatment, with different medical therapies targeting ATTR-CM and ATTR-PN.
ATTR is a progressive disease with no cure, so early intervention and treatment is an important part of managing symptoms and slowing disease progression regardless of a patient’s phenotype.
Sign up here to get the latest news, perspectives, and information about ATTR-CM sent directly to your inbox. Registration is free and only takes a minute.
