Screening of Fabry disease in patients with end-stage renal disease of unknown etiology: the first Thailand study

Abstract

We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease (ESRD) of an unknown origin. Venous blood samples were collected from ESRD patients for biochemical and molecular studies. Alpha-galactosidase A (α-GAL A) screening was performed from dried-blood spots using fluorometry. Molecular confirmation was performed using DNA sequencing of the GLA gene. A total of 142 male and female patients were included in this study. Ten patients (7.04%) exhibited a significant decrease in α-GAL A activity. There were no definitive pathogenic mutations observed in the molecular study. However, four patients revealed a novel nucleotide variant at c.1 -10 C>T, which was identified as a benign variant following screening in the normal population. In conclusion, the α-GAL A assay utilizing dried-blood spots revealed a significant false positive rate. There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.

Keywords

Fabry disease / end-stage renal disease (ESRD) / Alpha-galactosidase A (α-GAL A)

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Acknowledgements

This research was supported in grants by the Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (to OT and SP), and the Rare Genetic Disorder Fund, Ramathibodi Foundation (to OT), Bangkok, Thailand. Portions of this work were accepted as poster presentations at the 10^th Asia-Pacific Conference on Human Genetics, Kuala Lumpur, Malaysia, 5-8 December 2012 (PJ), and the International Congress of Inborn Errors of Metabolism, Barcelona, Spain, 3-6 September 2013 (OT). This work received a complimentary research award (to SP) for the oral presentation at the 44th-year-Ramathibodi Medical Conference, Bangkok, Thailand, 1-3 May 2013. We are grateful to Drs. Hui Zhou and Victor de Jesus, CDC, Atlanta, GA, USA, for providing the QC-DBS pools, to the nursing staffs at the Renal Disease Unit, Uttaradit Hospital, Uttaradit, Thailand, and the Hemodialysis Unit, Banphaeo Hospital- Prommitr Branch, Bangkok, Thailand, for assisting in clinical data and specimen collection, and to all the patients for their kind participation.

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