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

• Published in: Journal of inherited metabolic disease Vol. 33; no. 5; pp. 619 - 624
• Main Authors: Lin, Hsiang-Yu, Huang, Cheng-Hung, Yu, Hsiao-Chi, Chong, Kah-Wai, Hsu, Ju-Hui, Lee, Pi-Chang, Cheng, Kang-Hsiang, Chiang, Chuan-Chi, Ho, Huey-Jane, Lin, Shuan-Pei, Chen, Shih-Jen, Lin, Po-Kang, Niu, Dau-Ming
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01.10.2010; Springer Netherlands; Springer; Blackwell Publishing Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Albuminuria - enzymology; Albuminuria - genetics; alpha-Galactosidase - blood; alpha-Galactosidase - genetics; Asian Continental Ancestry Group - genetics; Biochemistry; Biological and medical sciences; Biomarkers - blood; China - ethnology; Clinical Enzyme Tests; Diagnostic Techniques, Ophthalmological; DNA Mutational Analysis; Echocardiography; Eye Diseases - enzymology; Eye Diseases - genetics; Fabry Disease - diagnosis; Fabry Disease - enzymology; Fabry Disease - ethnology; Fabry Disease - genetics; Female; Genetic Predisposition to Disease; Human Genetics; Humans; Hypertrophy, Left Ventricular - enzymology; Hypertrophy, Left Ventricular - genetics; Internal Medicine; Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mutation; Original Article; Pediatrics; Phenotype; Taiwan - epidemiology; Urinalysis; Young Adult; Asia; China; Taiwan; Fabry Disease; Ocular Manifestation; Enzyme Replacement Therapy; Left Ventricular Hypertrophy; Hypertrophic Cardiomyopathy; Human; Evaluation; Late; Asiatic; Nutrition; Enzyme; Hot spot; Metabolic diseases; Genetic disease; Assay; Age of onset; Chinese; Genetics; Clinical investigation; Diagnosis; Mutation
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-010-9166-7

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.