Published online before print July 24, 2009, doi: 10.1161/CIRCGENETICS.109.862920
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Original Articles |
High Incidence of the Cardiac Variant of Fabry Disease Revealed by Newborn Screening in the Taiwan Chinese Population
From the Institute of Clinical Medicine (H.Y.L., K.W.C., C.C.S., S.J.L., D.M.N.), National Yang-Ming University, Taipei; Department of Pediatrics (H.Y.L.), Mackay Memorial Hospital and Mackay Medicine, Nursing and Management College, Taipei; Department of Pediatrics (J.H.H., H.C.Y., C.H.H., P.C.L., C.H.K., K.H.C., D.M.N.), Taipei Veterans General Hospital, Taipei; Division of Cardiovascular Surgery (C.C.S.), Taipei Veterans General Hospital, Taipei; Division of Cardiology (S.J.L., C.H.C.), Department of Internal Medicine, Taipei Veterans General Hospital, Taipei; Cardiovascular Research Center (S.J.L., C.H.C.), National Yang-Ming University, Taipei; Department of Public Health (C.H.C.), National Yang-Ming University, Taipei; Neonatal Screening Center (C.C.C.), Chinese Foundation of Health, Taipei; Section of Newborn Screening (H.J.H.), Taipei Institute of Pathology, Taipei; and Department of Pathology (C.H.), Chang Gung Memorial Hospital, Linko, Chang Gung University, College of Medicine, Taoyuan, Taiwan.
Correspondence to Dau-Ming Niu, MD, PhD, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan. E-mail dmniu{at}vghtpe.gov.tw
Received March 5, 2009; accepted July 21, 2009.
Background— Fabry disease is a treatable lysosomal storage disorder, which is often misdiagnosed or belatedly diagnosed.
Methods and Results— To determine the disease incidence in the Taiwan Chinese population, a Fabry disease newborn screening study was initiated. A total of 110 027 newborns were screened by assaying the 
-galactosidase A (-Gal A) activity using dry blood spots. Low plasma -Gal A activity and presence of a Fabry mutation was demonstrated in 45 neonates (3 females). Eight different mutations were identified, including 3 known missense mutations (R112H, A143T, and R356W), 4 novel missense mutations (G104V, M296L, G360C, and K391T), and one known intronic mutation (IVS4+919G
A). The IVS4+919GA mutation was most common (82% of patients). A total of 20 maternal grandparents of infants harboring this intronic mutation were evaluated by echocardiography, mutation analysis and -Gal A activity assay. The intronic mutation was found in 9 grandfathers and 11 grandmothers. Of these grandparents, 3 grandfathers (33%) but none of the grandmothers had hypertrophic cardiomyopathy. Additionally, 16 males who had been diagnosed with idiopathic hypertrophic cardiomyopathy were screened by mutation analysis and -Gal A activity; 4 (25%) showed deficient plasma -Gal A activity in combination with the intronic mutation.
Conclusion— We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4+919GA among both newborns (
1 in 1600 males) and patients with idiopathic hypertrophic cardiomyopathy in the Taiwan Chinese population. The early identification of undiagnosed patients allows timely therapeutic intervention providing a better clinical outcome.
Key Words: hypertrophy • Fabry disease • hypertrophic cardiomyopathy • newborn screening • Taiwan Chinese population