Defining hATTR Amyloidosis

John L. Berk, MD: Hello, and thank you for joining this Neurology Live™ Peer Exchange titled, “Understanding Hereditary ATTR (hATTR) Amyloidosis and the Recent Advances in Management.” Hereditary amyloidosis is a rare form of amyloidosis that is passed down through families. It’s caused by an abnormal transthyretin protein made in the liver that misfolds to form amyloid.

In this Neurology Live™ Peer Exchange discussion, I’m joined by a panel of colleagues, all experts in the field of amyloidosis. Together we’ll discuss the diagnosis as well as use of the new therapeutic options, and will provide a practical perspective on how the recent data apply to your clinical practice.

I’m John Berk, assistant director of the Amyloidosis Center at Boston University School of Medicine in Boston, Massachusetts.

Participating today on our distinguished panel are: Dr James Dyck, the head of the Peripheral Nerve Research Laboratory and a professor of neurology at the Mayo Clinic in Rochester, Minnesota; Dr Akshay Desai, the director of the Cardiomyopathy and Heart Failure program at Brigham and Women’s Hospital in Boston, Massachusetts; Dr Michael Polydefkis, a professor of neurology and the director of the Cutaneous Nerve Lab at Johns Hopkins Medicine in Baltimore, Maryland.

Thank you so much for joining us. Let’s begin.

So the first thing I’d like to address is, What is hATTR amyloidosis, and how does it differ from wild-type ATTR disease? Both of these diseases are a result of misfolding of transthyretin. The distinction here is whether it’s a normal protein or an abnormal one. The abnormal protein is a result of an alteration in DNA. So the coding sequence has changed and the protein is considered mutated.

As a consequence, families inherit the disease and it’s important to provide surveillance over time. Does every [genotype]-positive person express clinical disease? Well, this is an important clinical concept called penetrance in genetics. And as a result, it turns out that everyone who has a mutation does not necessarily express the clinical manifestations of the disease. The prevalence of hATTR amyloidosis is a difficult topic, and I’d like to turn to Dr. Michael Polydefkis and actually Dr. Desai to provide a little bit of expertise on this.

Michael J. Polydefkis, MD: The exact prevalence isn’t entirely known, but estimates are that globally there are 50,000 patients with hATTR encompassing both the neuropathic and cardiogenic phenotypes. It’s estimated, in the United States, that there are probably at least 3000 patients with the disease. And certainly, there are hot spots around the globe with high prevalence rates.

John L. Berk, MD: Do you think that 3000 represents those who have polyneuropathy, or are we talking about polyneuropathy and cardiomyopathy?

Michael J. Polydefkis, MD: I think it’s a combination, and I think it’s also underestimated. It’s a disease that we often miss and have failed to think about historically. So I think the numbers are even larger than we think.