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JIMD Rep. 2014;17:83-90. doi: 10.1007/8904_2014_342. Epub 2014 Sep 16.

Uncertain diagnosis of fabry disease in patients with neuropathic pain, angiokeratoma or cornea verticillata: consensus on the approach to diagnosis and follow-up.

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Department of Internal Medicine, Division Endocrinology and Metabolism, Amsterdam lysosome centre 'Sphinx', Academic Medical Center, University of Amsterdam, Room F5-166, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.



Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the α-galactosidase A (GLA) gene may be unclear. This uncertainty often leads to considerable distress and inappropriate counselling and treatment. We developed a clinical approach for these individuals with an uncertain diagnosis of FD.


A document was presented to an FD expert panel with background information based on clinical experience and the literature, followed by an online survey and a written recommendation.


The 13 experts agreed that the recommendation is intended for individuals with neuropathic pain, AK and/or CV only, i.e. without kidney, heart or brain disease, with an uncertain diagnosis of FD. Only in the presence of FD-specific neuropathic pain (small fibre neuropathy with FD-specific pattern), AK (FD-specific localisations) or CV (without CV inducing medication), FD is confirmed. When these features have a non-specific pattern, there is insufficient evidence for FD. If no alternative diagnosis is found, follow-up is recommended.


In individuals with an uncertain diagnosis of FD, the presence of an FD-specific pattern of CV, AK or neuropathic pain is sufficient to confirm the diagnosis of FD. When these features are non-specific, a definite diagnosis cannot (yet) be established and follow-up is indicated. ERT should be considered only in those patients with a confirmed diagnosis of FD.

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