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Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: the FOCUS study
Albert A Hagège1, Eric Caudron, Thibaud Damy
1Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, University Paris Descartes, INSERM U 633, Paris, France. albert.hagege@egp.aphp.fr
Insights
Fabry disease (FD) cardiac variants are common in men with hypertrophic cardiomyopathy (HCM). A simple filter-paper test can identify FD, enabling early enzyme replacement therapy.
Area of Science:
- Cardiology
- Genetics
- Metabolic Diseases
Background:
- Fabry disease (FD) can cause left ventricular hypertrophy (LVH) that mimics hypertrophic cardiomyopathy (HCM).
- Early detection of FD allows for enzyme replacement therapy.
- Previous screening for FD in LVH patients using leucocyte alpha-galactosidase A (α-gal A) activity tests yielded 0-6% prevalence but was difficult to apply routinely.
Purpose of the Study:
- To systematically screen for FD in patients diagnosed with HCM (LVH ≥15 mm) in primary cardiology practice.
- To utilize a validated, physician-friendly α-gal A assay on dried blood spots (filter paper test).
Main Methods:
- Screened 392 adults (278 men) with a diagnosis of HCM for FD using a filter paper test.
- Confirmed low α-gal A results (≤40%) in nine men with a standard blood test.
Main Results:
- Diagnosed FD in four men (1.5% of cohort, 1.8% of men ≥40 years).
- No women were diagnosed with FD.
- Index cases presented with diffuse LVH, severe obstruction (1), and conduction block (3).
- Family screening identified eight additional FD cases.
- Genotyping was successful from filter paper DNA.
Conclusions:
- Cardiac variants of Fabry disease are not rare in male patients diagnosed with HCM.
- A simple filter-paper test can effectively identify these cases for targeted therapy.
- The filter-paper test shows low sensitivity in female patients.
Background:
Patients with Fabry disease (FD) show left ventricular hypertrophy (LVH) mimicking hypertrophic cardiomyopathy (HCM) of sarcomeric origin and might benefit, if detected early, from specific enzyme replacement therapy. The prevalence of FD in patients with LVH of 13 mm or greater, screened using the leucocyte alpha-galactosidase A (α-gal A) activity test, a technique that is difficult to apply routinely, ranged from 0% to 6%.
Objective:
To screen systematically for FD in patients with a diagnosis of HCM (LVH ≥15 mm) in primary cardiology practice, a validated, physician-friendly α-gal A assay was used on dried blood spots using a filter paper test.
Design And Patients:
A cohort of 392 adults (278 men) followed for HCM were screened for FD. A standard blood test was used for confirmation in nine men in whom the α-gal A result was 40% or less.
Results:
Four men (1.5%; 1.8% of men ≥40 years vs 0% <40 years; all with α-gal A <30%), but no women, were diagnosed with FD. Index cases presented with diffuse but asymmetric LVH, with severe obstruction in one case and frequent high-grade atrioventricular conduction block necessitating a pacemaker in three cases. Family screening identified eight additional cases. Genotyping was performed successfully on DNA extracted from the filter papers.
Conclusion:
In male patients diagnosed as having HCM, pure FD cardiac variants are not exceptional and can be specifically identified using a simple filter-paper test. The sensitivity of this test is low in female patients.
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