#AANAM – Diagnosis Still Challenging Without Disease Family History

Editor’s note: The FAP News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read more stories from the conference.

Diagnosing familial amyloid polyneuropathy (FAP) in people without a family history of the disease is still challenging, even though most patients show overt symptoms of the disorder, data from a genetic testing program showed.

Findings from the program also indicated that patients often visited multiple physicians before finally being directed to genetic testing, which ultimately led to correct diagnoses.

The researchers noted that a timely diagnosis is essential for early treatment.

Sami Khella, from the University of Pennsylvania, in Philadelphia, presented the findings in a poster titled “Clinical and Epidemiological Characteristics of Patients with TTR Mutations and Polyneuropathy Manifestations of Hereditary Transthyretin Amyloidosis: Insights from a Genetic Testing Program.” The poster was presented at the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting, recently held online.

Hereditary transthyretin amyloidosis (hATTR), also known as FAP, is caused by mutations in the TTR gene, which lead to the production and circulation of unstable forms of the TTR protein. These unstable proteins accumulate in various organs, disrupting their normal function.

Damage to peripheral nerves (polyneuropathy) and, in many cases, the muscles of the heart — called cardiomyopathy — are common. Of note, the peripheral nerves are those found outside the central nervous system, which includes the brain and the spinal cord.  These nerves relay information between the brain and the rest of the body, including the arms and legs.

An early diagnosis is key for easing disease progression and improving patients’ clinical outcomes.

Now, researchers in the U.S. and Canada, along with scientists from Ambry Genetics and Akcea Therapeutics, assessed the clinical symptoms of patients enrolled in the hATTR Compass program. That program provides confidential, free genetic testing and counseling to people suspected of having hATTR, or who have a family history of the disorder.

The program was launched by Ambry Genetics and Akcea, an affiliate of Ionis Pharmaceuticals, in 2018. It is available to people in the U.S., including Puerto Rico, and in Canada.

In total, data was analyzed from 718 people who had a disease-causing TTR mutation, as confirmed by genetic testing. Most patients (82%) carried the same mutation, called p.V142I, in the TTR gene. Almost half (48%) had more than one symptom consistent with polyneuropathy.

Among symptomatic patients, who had a mean age of 69, 59% were men and 70% were of African American descent.

The majority of patients with symptoms of polyneuropathy (61%) had no family history of hATTR. Approximately 66% of patients with symptoms were referred to the hATTR Compass program by a cardiologist, 9% by an internal medicine specialist, and 8% by a neurologist.

A total of 35 symptomatic patients (10%) reported that they had gone to more than two medical appointments with different physicians (average 2.4) before going to a genetic consultation.

In symptomatic patients, evidence of heart disease also was common, with symptoms observed in 79% of patients. These individuals initially had symptoms of polyneuropathy that included sensory (59%), autonomic (34%), and motor (29%) impairments.

Overall, these findings highlight how “diagnosis of hATTR amyloidosis is challenging, as many patients see multiple doctors before being diagnosed and many do not have a known family history of hATTR,” the researchers wrote.

“Recognizing hATTR symptoms and performing genetic testing facilitates timely diagnosis” and is crucial for early treatment, they concluded.