Patients with hereditary transthyretin amyloidosis (hATTR) commonly present with a specific set of signs and symptoms, known as “red flags,” at the time of diagnosis, according to a study conducted in Spain that was recently published in Neurología.

“Presence of red flags in a patient with symmetrical sensorimotor polyneuropathy should serve as a warning sign, and lead to targeted diagnosis to rule out hATTR, independently of age of onset or geographical region,” the researchers concluded. “This is particularly important considering that early treatment appears to be associated with a better response.”

All patients presented with at least 1 red flag and they had a median of 4 at the time of diagnosis. Moreover, the researchers identified 3 or more red flags in all 6 patients with early-onset disease and 22 of the 24 patients with late-onset disease. The researchers did not find statistically significant differences in the number of red flags at the time of diagnosis between patients with early-onset disease and those with late-onset disease or between patients with and without the Val30Met (V30M) mutation.

Read more about the diagnosis of hATTR

The most common red flags at the time of diagnosis were a family history of peripheral neuropathy (70%), early autonomic dysfunction (56.7%), a family history of heart disease (50%), bilateral carpal tunnel syndrome (50%), gastrointestinal symptoms (46.7%), asymptomatic electrocardiogram, echocardiography, or DPD-scintigraphy alterations (43.3%), and cardiac symptoms (40%). In addition, 26.7% of patients experienced unintended weight loss, 10% had a family history of gastrointestinal disease, 6% had unilateral carpal tunnel syndrome, and 3.3% suffered from kidney failure. Vitreous opacification was not observed in any patients.

The study enrolled 30 patients diagnosed with hATTR from a nonendemic area in Spain. Most patients (80%) had late-onset disease. More than half of the patients (60%) tested positive for the V30M mutation.

The use of red flags as diagnostic markers for hATTR is not universally accepted, as previous studies have questioned their reliability. This study is limited by the small sample size.

Reference

Silva-Hernández L, Horga Hernández A, Valls Carbó A, Guerrero Sola A, Montalvo-Moraleda MT, Galán Dávila L. Red flags in patients with hereditary transthyretin amyloidosis at diagnosis in a non-endemic area of Spain. Neurologia (Engl Ed). Published online November 15, 2022. doi:10.1016/j.nrleng.2020.06.015