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

• Published in: Heart (British Cardiac Society) Vol. 97; no. 2; pp. 131 - 136
• Main Authors: Hagège, Albert A, Caudron, Eric, Damy, Thibaud, Roudaut, Raymond, Millaire, Alain, Etchecopar-Chevreuil, Caroline, Tran, Thi-Chien, Jabbour, Firas, Boucly, Catherine, Prognon, Patrice, Charron, Philippe, Germain, Dominique P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Cardiovascular Society 01.01.2011; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Accuracy; Adolescent; Adult; Aged; alpha-Galactosidase - analysis; alpha-Galactosidase - genetics; Biological and medical sciences; Cardiac variant; Cardiology; Cardiology. Vascular system; Cardiomyopathy; cardiomyopathy hypertrophic; Cardiomyopathy, Hypertrophic - complications; Clinical Enzyme Tests - methods; Cohort Studies; Early Diagnosis; Enzymes; Errors of metabolism; Fabry disease; Fabry Disease - diagnosis; Family medical history; Female; filter-paper test; genetics; Heart; Humans; Hypertension; hypertrophic cardiomyopathy; Laboratories; Leukocytes - enzymology; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical sciences; Metabolic diseases; Middle Aged; Mutation; Myocarditis. Cardiomyopathies; screening; Sensitivity and Specificity; Shipments; Young Adult; Human; Nervous system diseases; Fabry disease; Metabolic diseases; Cardiovascular disease; Lipids; Patient; Filter paper; Medical screening; Enzymopathy; Myocardial disease; Genetic disease; Vascular disease; Heart disease; Hypertrophic cardiomyopathy; Circulatory system; Cardiology; Lipoidosis
• ISSN: 1355-6037; 1468-201X
• DOI: 10.1136/hrt.2010.200188

BackgroundPatients 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%.ObjectiveTo 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 patientsA 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.ResultsFour 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.ConclusionIn 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.