Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic

Author:

Di Stefano Vincenzo1ORCID,Lupica Antonino1,Alonge Paolo1,Pignolo Antonia1,Augello Sofia Maria1,Gentile Francesca1,Gagliardo Andrea1,Giglia Francesca2,Brinch Daniele3,Cappello Maria3,Di Lisi Daniela4,Novo Giuseppina4,Borgione Eugenia5,Scuderi Carmela5,Brighina Filippo1

Affiliation:

1. Section of Neurology, Department of Biomedicine Neuroscience, and Advanced Diagnostics, University of Palermo Palermo Italy

2. Unit of Neurology With Stroke Unit S. Giovanni di Dio Hospital Agrigento Italy

3. Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties University of Palermo Palermo Italy

4. Section of Cardiology, Department of Health Promotion, Mother and Child Care Internal Medicine, and Medical Specialties, University of Palermo Palermo Italy

5. Unit of Neuromuscular Diseases Oasi Research Institute, IRCCS Troina Italy

Abstract

AbstractBackground and purposeHereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils.MethodsA prospective systematic genetic screening for ATTRv‐PN was proposed in patients presenting with a sensory–motor idiopathic polyneuropathy and two or more “red flags” among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients.ResultsIn the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv‐PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv‐PN patients and 26 presymptomatic carriers) among 84 first‐degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy.ConclusionsA systematic screening for ATTRv‐PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv‐PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow‐up at the clinical onset.

Funder

Alnylam Pharmaceuticals

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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