Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: the FOCUS study.
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.


METHODS
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.


CONCLUSIONS
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.
Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, University Paris Descartes, INSERM U 633, Paris, France. albert.hagege@egp.aphp.fr
Albert A
AA
Hagège
Eric
E
Caudron
Thibaud
T
Damy
Raymond
R
Roudaut
Alain
A
Millaire
Caroline
C
Etchecopar-Chevreuil
Thi-Chien
TC
Tran
Firas
F
Jabbour
Catherine
C
Boucly
Patrice
P
Prognon
Philippe
P
Charron
Dominique P
DP
Germain
D000293:Adolescent; D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications*; D004796:Clinical Enzyme Tests / Q000379:methods; D015331:Cohort Studies; D042241:Early Diagnosis; D000795:Fabry Disease / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D055815:Young Adult; D000519:alpha-Galactosidase / Q000032:analysis* / Q000235:genetics
D000519:alpha-Galactosidase