Uncertain diagnosis of Fabry disease: Consensus recommendation on diagnosis in adults with left ventricular hypertrophy and genetic variants of unknown significance
SourceInternational Journal of Cardiology, 177, 2, (2014), pp. 400-408
Article / Letter to editor
Display more detailsDisplay less details
International Journal of Cardiology
SubjectRadboudumc 0: Other Research RIHS: Radboud Institute for Health Sciences
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 alpha-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 >12mm), 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>15mm) <20years 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.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.