Summary
Fabry disease is a complex, multisystemic and clinically heterogeneous disease with prominent urinary excretion of globotriaosylceramide (Gb3), the principal substrate of the deficient enzyme, α-galactosidase A. Some measure of specific treatment is possible with enzyme replacement therapy, which can be applied safely and effectively to Fabry patients. Incidence estimations of Fabry disease vary widely from 1:55 000 to 1:3000 male births. The true incidence is likely to be higher than originally thought, owing to the existence of milder variants of the disease. The main complications of Fabry disease are a 100-fold increased risk of ischaemic stroke, cardiac disease, a wide variety of arrhythmias, valvular dysfunction and cardiac vascular disease, as well as progressive renal failure usually associated with significant proteinuria. These clinical manifestations are non-specific and are often mistaken for symptoms of other disorders, thus complicating the confirmation of diagnosis. Other clinical features of the disease are often absent (angiokeratoma), subtle (corneal opacities and hypohidrosis), or unaccompanied by specific physical findings (acroparaesthesias) indicating the true nature of the underlying disease. We propose the hypothesis that α-galactosidase A deficiency is a modifiable cardiovascular risk factor in the general population. This hypothesis may be tested by a non-invasive high-risk screening protocol for Fabry patients with ischaemic strokes and a variety of cardiac, and renal complications. These patients would benefit from diagnosis, appropriate treatment, follow-up and surveillance. Early detection of Fabry patients would also benefit affected relatives, many of whom do not have a clear diagnosis of their clinical condition.
Abbreviations
- α-Gal A:
-
alpha-galactosidase A
- Gb3 :
-
globotriaosylceramide (GL-3 or CTH (ceramide trihexoside))
- LC-MS/MS:
-
liquid chromatography–tandem mass spectrometry
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Acknowledgements
We thank all Fabry patients who throughout the years inspired us to devise methodologies, clinical studies or protocols in order to better understand the pathophysiology of this complex disease. We would also like to acknowledge Waters Corporation (Milford, MA, USA) for their continued scientific and technical support in mass spectrometry applications.
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Communicating editor: Douglas Brooks
Competing interests: None declared
References to electronic databases: Fabry disease: OMIM 301500. Alpha-galactosidase A (α-Gal A) (EC 3.2.1.22).
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Auray-Blais, C., Millington, D.S., Young, S.P. et al. Proposed high-risk screening protocol for Fabry disease in patients with renal and vascular disease. J Inherit Metab Dis 32, 303–308 (2009). https://doi.org/10.1007/s10545-009-1055-6
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DOI: https://doi.org/10.1007/s10545-009-1055-6