Hereditary Transthyretin Amyloidosis Patients Can Be Identified Through a Genomic Screening Program

No evidence-based guidelines for the management of transthyretin (TTR) variant–positive individuals currently exist, yet experts emphasize the need for early identification and a multidisciplinary approach to manage at-risk patients, so surveillance strategies can be implemented. There is a high frequency of the variant V142I among African-American and Hispanic/Latinx populations that is often overlooked, which contributes to diagnostic delays. In ≤4% of African-American and 1% of Hispanic/Latinx individuals, the TTR V142I variant is linked with hereditary transthyretin amyloidosis (hATTR). This variant increases heart failure risk. Health disparities are exacerbated by delayed and missed diagnoses in these frequently underserved populations.

Soper and colleagues investigated whether population-based genomic screening could detect individuals at increased risk for hATTR and encourage the adoption of risk management strategies. They reviewed BioMe Biobank records in New York City to identify patients who received TTR V142I results through a genomic screening program that was in the pilot stage. Patients who had submitted records to the database had done so with informed consent. A retrospective medical record review was used to assess patients for the presence of hATTR-related systemic features, determine the extent of recommended follow-up uptake, and evaluate short-term outcomes.

Of the 32 individuals who received a TTR V142I result, 17 were African American and 15 were Hispanic/Latinx. The median age of participants was 57 years and 81% were female. A previous diagnosis of hATTR was not present in any of the patients. Over half (56%) of the patients had hATTR-related systemic features; these included 13% with heart failure, 31% with carpal tunnel syndrome, and 31% with spinal stenosis. Within 8 months, more than half (56%) followed up with a cardiologist; generally, the cardiac evaluation that was recommended based on risk factors and age included baseline echocardiogram for all V142I-positive individuals and Tc-99m-pyrophosphate scintigraphy with single-photon emission computerized tomography imaging. A diagnosis of hATTR was made in 1 case.

hATTR risk can be identified through genomic screening and this can guide management early on, preventing potential diagnostic and treatment delays. The investigators’ goal of assessing whether genomic screening could help identify patients at risk for hATTR and prompt follow-up visits with specialists was met. The genomic screening program proved useful in evaluating medical records for hATTR-related systemic features, recommended follow-up uptake, and short-term outcomes.

This study reinforces the potential for translating genomic risk information into care for diverse patient populations. Understanding the natural history and progression of the disease is vital to preventing diagnostic delays. Early diagnosis is particularly critical as therapeutics are being developed that prevent new cardiac amyloid deposition but do not ameliorate existing amyloid deposits.

Source: Soper ER, Suckiel SA, Braganza GT, et al. Genomic screening identifies individuals at high risk for hereditary transthyretin amyloidosis. J Pers Med. 2021;11:49.

Related Items

Subscribe to Amyloidosis News

Stay up to date with Amyloidosis News & updates by subscribing to receive the free AMN e‑Newsletter.

I'd like to receive: