title: Enzyme assay and clinical assessment in subjects with a Chinese hotspot late-onset Fabry mutation (IVS4 + 919G→A).
abstract: Newborn screening for Fabry disease in Taiwan Chinese has revealed a high incidence of the late-onset GLA mutation IVS4 + 919G→A (∼1 in 1,500-1,600 males). We studied 94 adults with this mutation [22 men, 72 women; mean age: men 57.8 ± 6.0 (range 42-68), women 39.1 ± 14.1 years (range 19-82)]. Plasma α-galactosidase A activity assay was 10.4 ± 11.2% of normal in the men and 48.6 ± 19.5% of normal in the women. Echocardiography in 90 of the adults revealed left ventricular hypertrophy (LVH) in 19 (21%), including 14 of 21 men (67%) and 5 of 69 women (7%). Microalbuminuria, based on the urine albumin-to-creatinine ratio measured on at least two occasions, was present in 17 of 86 subjects (20%) (men: 5/20, 25%; women 12/66, 18%). At least one ocular manifestation consistent with Fabry disease was present in 41 of 52 subjects (79%) who underwent ophthalmologic examination, including 8 (15%) with conjunctival vessel tortuosity, 15 (29%) with cornea verticillata, 10 (19%) with Fabry cataract, and 34 (65%) with retinal vessel tortuosity. Among subjects over 40 years of age, men were more likely than women to have LVH [14/21 (67%) vs 5/25 (20%), p < 0.001]. Cardiovascular, renal and ocular abnormalities are highly prevalent in adult Taiwan Chinese subjects with the Fabry mutation IVS4 + 919G→A. Our findings contribute to the limited understanding of the course of this late-onset disease variant and underscore the need for close follow up in such patients.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Lin
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Huang
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Yu
authors.forename: Kah-Wai
authors.initials: KW
authors.lastname: Chong
authors.forename: Ju-Hui
authors.initials: JH
authors.lastname: Hsu
authors.forename: Pi-Chang
authors.initials: PC
authors.lastname: Lee
authors.forename: Kang-Hsiang
authors.initials: KH
authors.lastname: Cheng
authors.forename: Chuan-Chi
authors.initials: CC
authors.lastname: Chiang
authors.forename: Huey-Jane
authors.initials: HJ
authors.lastname: Ho
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Po-Kang
authors.initials: PK
authors.lastname: Lin
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000201:enzymology / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002681:China / Q000208:ethnology; D004796:Clinical Enzyme Tests; D004252:DNA Mutational Analysis; D003941:Diagnostic Techniques, Ophthalmological; D004452:Echocardiography; D005128:Eye Diseases / Q000201:enzymology / Q000235:genetics; D000795:Fabry Disease / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D013624:Taiwan / Q000453:epidemiology; D016482:Urinalysis; D055815:Young Adult; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
chemical_list: D015415:Biomarkers; D000519:alpha-Galactosidase
references.citation: Hum Mutat. 2009 Oct;30(10):1397-405
references.pmid: 19621417
references.citation: Circ Cardiovasc Genet. 2009 Oct;2(5):450-6
references.pmid: 20031620
references.citation: J Am Soc Nephrol. 2004 May;15(5):1323-9
references.pmid: 15100373
references.citation: Am J Cardiol. 1987 Apr 15;59(9):956-60
references.pmid: 2952002
references.citation: Am J Hum Genet. 2002 Apr;70(4):994-1002
references.pmid: 11828341
references.citation: Hum Mutat. 2005 Mar;25(3):299-305
references.pmid: 15712228
references.citation: Circulation. 2009 Feb 3;119(4):524-9
references.pmid: 19153271
references.citation: Hum Genomics. 2006 Mar;2(5):297-309
references.pmid: 16595074
references.citation: Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266
references.pmid: 11904577
references.citation: Circulation. 2002 Mar 26;105(12):1407-11
references.pmid: 11914245
references.citation: Genet Med. 2007 Jan;9(1):34-45
references.pmid: 17224688
references.citation: J Am Coll Cardiol. 2007 Dec 18;50(25):2399-403
references.pmid: 18154965
references.citation: Clin Exp Ophthalmol. 2005 Apr;33(2):164-8
references.pmid: 15807825
references.citation: Ann Intern Med. 2007 Jan 16;146(2):77-86
references.pmid: 17179052
references.citation: J Pediatr. 2008 Apr;152(4):563-70, 570.e1
references.pmid: 18346516
references.citation: Lancet. 2005 Nov 19;366(9499):1794-6
references.pmid: 16298216
references.citation: Kidney Int. 2003 Sep;64(3):801-7
references.pmid: 12911529
references.citation: J Med Genet. 2006 Apr;43(4):347-52
references.pmid: 16227523
references.citation: J Lab Clin Med. 1973 Feb;81(2):157-71
references.pmid: 4683418
references.citation: Br J Ophthalmol. 2007 Feb;91(2):210-4
references.pmid: 16973664
references.citation: Ophthalmic Genet. 2003 Sep;24(3):129-39
references.pmid: 12868031
references.citation: Clin Nephrol. 2005 Oct;64(4):281-7
references.pmid: 16240899
references.citation: N Engl J Med. 1995 Aug 3;333(5):288-93
references.pmid: 7596372
references.citation: JAMA. 1999 Jan 20;281(3):249-54
references.pmid: 9918480
references.citation: Mol Genet Metab. 2008 Feb;93(2):112-28
references.pmid: 18037317
references.citation: Arch Ophthalmol. 1979 Apr;97(4):671-6
references.pmid: 106811
references.citation: Lancet. 2008 Oct 18;372(9647):1427-35
references.pmid: 18940466
references.citation: Zhonghua Yi Xue Za Zhi (Taipei). 1994 Nov;54(5):368-72
references.pmid: 7834562