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Enzyme assay and clinical assessment in subjects with a Chinese hotspot late-onset Fabry mutation (IVS4 + 919G→A)

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Journal of Inherited Metabolic Disease

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.

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Acknowledgements

We would like to express our sincere thanks to Dr. Hans Ebels for his critical review and valuable comments and Ms. Tsai-Feng Ho for her professional assistance in biostatistics. This work was supported by Taipei Veterans General Hospital (V99C1-147).

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Authors and Affiliations

  1. Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan

    Hsiang-Yu Lin, Cheng-Hung Huang, Kah-Wai Chong & Dau-Ming Niu

  2. Department of Pediatrics, Mackay Memorial Hospital and Mackay Medicine, Nursing and Management College, Taipei, Taiwan

    Hsiang-Yu Lin & Shuan-Pei Lin

  3. Department of Pediatrics, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan

    Cheng-Hung Huang, Hsiao-Chi Yu, Ju-Hui Hsu, Pi-Chang Lee, Kang-Hsiang Cheng & Dau-Ming Niu

  4. Neonatal Screening Center, Chinese Foundation of Health, Taipei, Taiwan

    Chuan-Chi Chiang

  5. Section of Newborn Screening, Taipei Institute of Pathology, Taipei, Taiwan

    Huey-Jane Ho

  6. Department of Ophthalmology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan

    Shih-Jen Chen & Po-Kang Lin

  7. School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan

    Shih-Jen Chen & Po-Kang Lin

  8. Graduate Institute of Biomedical Electronic and Bioinformatics, National Taiwan University, Taipei, Taiwan

    Po-Kang Lin

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  1. Hsiang-Yu Lin
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  2. Cheng-Hung Huang
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  13. Dau-Ming Niu
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Corresponding authors

Correspondence to Po-Kang Lin or Dau-Ming Niu.

Additional information

Communicated by: Olaf Bodamer

Competing interest: None declared.

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Lin, HY., Huang, CH., Yu, HC. et al. Enzyme assay and clinical assessment in subjects with a Chinese hotspot late-onset Fabry mutation (IVS4 + 919G→A). J Inherit Metab Dis 33, 619–624 (2010). https://doi.org/10.1007/s10545-010-9166-7

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  • DOI: https://doi.org/10.1007/s10545-010-9166-7

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