<p>Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines</p>

Abstract

The outlook for transthyretin amyloidosis (ATTR) is changing with the availability of new and emerging treatments. ATTR now appears to be more common than previously thought and is no longer viewed as an obscure diagnosis with a grim prognosis. Now more than ever, there is growing emphasis on the need for early diagnosis because the treatments appear to be most effective if started in earlier stages of the disease. Diagnosing ATTR is a challenge as it may initially present with nonspecific symptoms and it is often thought of as a diagnosis of exclusion. Increased awareness is imperative as new treatments offer hope and have the potential to change the disease trajectory. ATTR commonly presents with neurological and cardiac features. Transthyretin (TTR) is a protein produced in the liver which misfolds either due to genetic mutations or due to aging and results in deposition of amyloid fibrils in organs and tissues. Apart from the traditional imaging modalities, newer techniques including echocardiographic strain imaging, magnetic resonance imaging (MRI), and nuclear scintigraphy, as well as the increased availability of genetic testing are aiding in making a timely diagnosis. In this review, we present the current understanding of the ATTR disease process, diagnostic and surveillance approaches, newer treatment modalities, and the future directions.

Changes in nerve conduction studies predate clinical symptoms onset in early onset Val30Met hereditary ATTR amyloidosis

“…In endemic areas, diagnosis of conversion to symptomatic in ATTRV30M‐PN relies mainly in clinical symptoms [35,36], although some authors recommend serial evaluations, and a change from baseline in nerve conduction studies as a criterion for conversion [19]. In our experience, at the time of symptomatic conversion, most of ATTRV30M‐PN carriers still have nerve conduction values within normal range for age and gender.…”

Late-Onset Hereditary Transthyretin Amyloidosis Val30Met in an Elderly Person in a Non-Endemic Area

“…For hATTR patients, treatments in early-onset disease, stage I (patients can walk) and stage II (patients can walk with assistance) are available to help slow the progression of neuropathy and can improve the quality of life of patients. 16 , 17 Outside Japan, the choice of drug therapy is first-line treatment, such as TTR stabilizing agent (tafamidis) and RNAi drug patisiran. However, liver transplantation remains a first-line treatment due to the positive results of liver transplantation in Japan (better life expectancy and higher survival rate).…”

Addressing the routine failure to clinically identify monogenic cases of common disease

“…One of these, cardiac amyloidosis, is now recognized as a frequently missed diagnosis in African Americans with heart failure [ 55 , 56 ]. With the availability of new FDA-approved targeted therapies that delay amyloidosis progression [ 57 ], genetic testing for TTR V142I, a founder variant present in 3–4% of African Americans, could improve outcomes for this disease [ 58 – 60 ]. Importantly, although the optimization of clinical care is only enabled by the accurate identification of such monogenic forms of common disease, the vast majority of these go unrecognized in routine clinical care today.…”