Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 177, Issue 2, Pages 400-408Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2014.09.001
Keywords
Fabry disease; Left ventricular hypertrophy; Hypertrophic cardiomyopathy; Consensus; Diagnosis
Categories
Funding
- TI Pharma [T6-504]
- Shire
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Background: Screening in subjects with left ventricular hypertrophy (LVH) reveals a high prevalence of Fabry disease (FD). Often, a diagnosis is uncertain because characteristic clinical features are absent and genetic variants of unknown significance (GVUS) in the a-galactosidase A (GLA) gene are identified. This carries a risk of misdiagnosis, inappropriate counselling and extremely expensive treatment. We developed a diagnostic algorithm for adults with LVH (maximal wall thickness (MWT) of >12 mm), GLA GVUS and an uncertain diagnosis of FD. Methods: A Delphi method was used to reach a consensus between FD experts. We performed a systematic review selecting criteria on electrocardiogram, MRI and echocardiography to confirm or exclude FD. Criteria for a definite or uncertain diagnosis and a gold standard were defined. Results: A definite diagnosis of FD was defined as follows: a GLA mutation with <= 5% GLA activity (leucocytes, mean of reference value, males only) with >= 1 characteristic FD symptom or sign (neuropathic pain, cornea verticillata, angiokeratoma) or increased plasma (lyso) Gb3 (classical male range) or family members with definite FD. Subjects with LVH failing these criteria have a GVUS and an uncertain diagnosis. The gold standard was defined as characteristic storage in an endomyocardial biopsy on electron microscopy. Abnormally low voltages on ECG and severe LVH (MWT >15 mm) <20 years exclude FD. Other criteria were rejected due to insufficient evidence. Conclusions: In adults with unexplained LVH and a GLA GVUS, severe LVH at young age and low voltages on ECG exclude FD. If absent, an endomyocardial biopsy with electron microscopy should be performed. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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