Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry |
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| Authors: | Angéla Dajnoki György Fekete Joan Keutzer Joseph J. Orsini Victor R. De Jesus Yin-Hsiu Chien Wuh-Liang Hwu Zoltan Lukacs Adolf Mühl X. Kate Zhang Olaf Bodamer |
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| Affiliation: | 1. Genetics and Molecular Pathology, SA Pathology [at Women''s and Children''s Hospital], 72 King William Road, North Adelaide, South Australia 5006, Australia;2. Department of Paediatrics, University of Adelaide, Adelaide, South Australia 5005, Australia;3. Department of Clinical Haematology, Royal Melbourne Hospital and Department of Medicine, Australia;4. University of Melbourne, Parkville, Victoria 3050, Australia;1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;2. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan;3. Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan;4. Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan;5. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan;6. Feng Chi Biotech Corp., Taipei, Taiwan;7. Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan;8. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan;9. VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan |
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| Abstract: | BackgroundFabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of α-galactosidase A (GLA). We evaluated a tandem mass spectrometry method to measure GLA activity.MethodsOne 3.2 mm punch from a dried blood spot sample (DBS) was incubated with substrate and internal standard in the reaction buffer for 22 h. The resulting product was quantified against internal standard using MS/MS.ResultsThe median GLA activity of male newborn DBS (N = 5025) was 9.85 ± 6.4 µmol/h/l (CI 95% is 9.67–10.02 µmol/h/l); The median GLA activity of female newborns (N = 4677) was 10.2 ± 6.3 µmol/h/l (CI 95% is 10.02–10.38 µmol/h/l). The difference between the two subgroups is within assay analytical variation. The GLA activities in the DBS samples from 9 juvenile and adult males with previously identified FD were below 1.64 µmol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 µmol/h/l. In 5 (16%) females GLA activities were above the 0.5th percentile of lower limit of CI 95% at 3.18 µmol/h/l.ConclusionsThe MS/MS method for Fabry disease newborn screening is robust and can be readily multiplexed with other lysosomal disorders such as Pompe, Gaucher, Niemann–Pick, and Krabbe diseases. |
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