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Updated: Jun 14, 2026
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry
Angéla Dajnoki1, György Fekete, Joan Keutzer
1Department of General Paediatrics and Neonatology, University Children's Hospital, Vienna, Austria.
Background:
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A (GLA). We evaluated a tandem mass spectrometry method to measure GLA activity.
Methods:
One 3.2mm 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.
Results:
The median GLA activity of male newborn DBS (N=5025) was 9.85 + or - 6.4 micromol/h/l (CI 95% is 9.67-10.02 micromol/h/l); The median GLA activity of female newborns (N=4677) was 10.2 + or - 6.3 micromol/h/l (CI 95% is 10.02-10.38 micromol/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 micromol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 micromol/h/l. In 5 (16%) females GLA activities were above the 0.5th percentile of lower limit of CI 95% at 3.18 micromol/h/l.
Conclusions:
The 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.
