Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner
Open Access
- 23 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Family Practice
- Vol. 21 (1), 1-12
- https://doi.org/10.1186/s12875-020-01252-4
Abstract
Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.Keywords
Funding Information
- Amyloidosis Research Consortium
This publication has 83 references indexed in Scilit:
- Guideline of transthyretin-related hereditary amyloidosis for cliniciansOrphanet Journal of Rare Diseases, 2013
- THAOS – The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosisCurrent Medical Research and Opinion, 2012
- Transthyretin (TTR) Cardiac AmyloidosisCirculation, 2012
- Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathyNeurogastroenterology & Motility, 2012
- Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areasJournal of Neurology, Neurosurgery & Psychiatry, 2012
- Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variantEuropean Heart Journal, 2011
- Diagnosis of sporadic transthyretin Val30Met familial amyloid polyneuropathy: a practical analysisAmyloid, 2011
- A prospective evaluation of the transthyretin Ile122 allele frequency in an African-American populationAmyloid, 2005
- Gastrointestinal dysfunction in familial amyloidotic polyneuropathy (ATTR Val3 et) - comparison of Swedish and Japanese patientsAmyloid, 1999
- Revised transthyretin Ile 122 allele frequency in African-AmericansHuman Genetics, 1996