Enzyme assay and clinical assessment in subjects with a Chinese hotspot late-onset Fabry mutation (IVS4 + 919G→A).
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.
Lin
Hsiang-Yu
HY
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Huang
Cheng-Hung
CH
Yu
Hsiao-Chi
HC
Chong
Kah-Wai
KW
Hsu
Ju-Hui
JH
Lee
Pi-Chang
PC
Cheng
Kang-Hsiang
KH
Chiang
Chuan-Chi
CC
Ho
Huey-Jane
HJ
Lin
Shuan-Pei
SP
Chen
Shih-Jen
SJ
Lin
Po-Kang
PK
Niu
Dau-Ming
DM
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*
D015415:Biomarkers; D000519:alpha-Galactosidase
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