Clinical And Genetic Profile Of Hereditary Transthyretin (ATTRv) Amyloidosis In The Middle East: A Single-Center Report

Abstract

Background and Purpose: Transthyretin (ATTR) amyloidosis, including wild-type (ATTRwt) and hereditary (ATTRv) forms, is a rare but increasingly recognized disease. This first report from the Middle East presents our experience diagnosing ATTRv amyloidosis at the Abdali National Amyloidosis Center

Methods: All referred patients underwent comprehensive evaluation. ATTR amyloidosis was established by a Perugini grade 2 or 3 positive pyrophosphate (PYP) scan, with exclusion of light chain monoclonality by serum and urine immunofixation and free light chain assay. Confirmed cases subsequently underwent genetic testing for TTR mutations

Results: Between July 2021 and October 2025, 21 patients with ATTRv amyloidosis were identified (19 men, 2 women), mean age 59 years (range 40-75). Fifteen were from Iraq, two from Libya, two from Jordan, and one each from Sudan and Syria. Twenty patients had a Perugini grade 3 positive PYP scan and in one patient with the Thr60Ala mutation, the grade was 0. Mutations included Thr60Ala (n=16, Northern Iraq, Jordan, Syria), Lys55Asn (n=2, Libya), Val142Ile (n=1, Sudan), Ser43Asn (n=1, Iraq), and Val50Met (n=1, Jordan). Clinical features were heart failure in 16, neuropathy (peripheral/autonomic) in 14, diarrhea in 9, and weight loss (6-35 kg) in 14. Symptom duration ranged from 4 months to 6 years. Electrocardiographic findings included low voltage (n=7), atrial fibrillation (n=3), QRS prolongation (n=10), and permanent pacemaker implantation (n=4). All had elevated BNP/NT-proBNP and hs-troponin. Echocardiography showed left ventricular hypertrophy in 20 and pericardial effusion in 14; left ventricular ejection fraction ranged from 28-69%. Genetic screening of 16 relatives (7 men, 9 women) identified 12 carriers, with further workup confirming ATTRv in one

Conclusions: This first report from the Middle East highlights the clinical profile and genetics of ATTRv amyloidosis in the region, underscoring the need for greater awareness and continued research.