Genetic counseling key for early treatment for at-risk people in FAP

Getting genetic testing offers the option of early treatment, if needed

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Getting genetic counseling can encourage people at risk for hereditary transthyretin amyloidosis to have genetic testing and know they have the option to seek early treatment if needed, a study suggests. Hereditary transthyretin amyloidosis is a group of diseases that include familial amyloid polyneuropathy (FAP).

Having genetic testing can give rise to some difficult emotions, but receiving psychological support along with genetic counseling may help patients deal with stress and ease feelings of anxiety or depression, according to the researchers in “Genetic counselling for at-risk family members with hereditary transthyretin amyloidosis: data from a single-centre study,” which was published in The Journal of Protein Folding Disorders.

“We hope many patients, at-risk individuals, and medical professionals can understand the significance of appropriately promoting this type of approach,” Katsuya Nakamura, MD, PhD, the study’s first author and an assistant professor at Shinshu University Hospital in Japan, said in a university press release.

Hereditary transthyretin amyloidosis, or hATTR, occurs due to mutations in the TTR gene that can be passed down in families. The mutations cause the transthyretin protein to fold incorrectly and form toxic deposits, which can damage tissues and organs, including the nerves and heart.

FAP, also known as hereditary transthyretin amyloidosis with polyneuropathy, is a type of hATTR marked by neurological symptoms due to toxic transthyretin aggregates building up mainly in the nerves outside the brain and spinal cord. When the deposits accumulate primarily in the heart, the condition is called hereditary transthyretin amyloid cardiomyopathy. Sometimes, hATTR manifests as both polyneuropathy and cardiomyopathy.

There are several disease-modifying treatments available for FAP and other forms of hATTR. The therapies are most effective when started as early as possible in the disease.

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Genetic screening can help diagnose FAP when polyneuropathy evident 

Benefit of genetic counseling in FAP

As the diseases can manifest only in adulthood, it’s important to screen family members of patients to understand whether they carry a disease-causing mutation and to start early treatment.

Genetic counseling can help people concerned about the genetic risk of disease to make informed decisions about genetic testing and to help understand treatment options. Not everyone at risk seeks genetic counseling, however.

“We still encounter patients who are hesitant to share their genetic information with their families,” Nakamura said. “Therefore, we decided to investigate the extent to which the at-risk family members of patients benefit from appropriate genetic care through genetic counseling.”

Nakamura’s team retrospectively analyzed data from 202 people who received genetic counseling for hATTR at Shinshu University Hospital from April 1998 to March 2021. Of the 103 people with a family history of hATTR, but showed no symptoms, 83 (80.6%) had genetic testing. Positive results were seen for 33 of them (39.8%).

Further testing confirmed the presence of toxic transthyretin deposits in 11 of the 33 carriers, who were started on disease-modifying treatments to slow the disease, even in its presymptomatic stages when symptoms hadn’t yet manifested.

Toxic transthyretin deposits were found at a median age of 32 for the people who carried the Val30Met mutation, the most common genetic cause of FAP.

With treatment, blood levels of transthyretin decreased over time at a rate of about 1.2 mg/dL per year.

“The number of presymptomatic carriers detected using targeted genetic approaches is expected to increase,” Nakamura said, adding “developing a less invasive and simpler method for monitoring that can be performed at any facility other than specialized amyloidosis centers is imperative.”

The researchers said “psychosocial support should be considered” among a collaboration of “geneticists/genetic counsellors and psychologists.”