Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry
Journal
Clinica Chimica Acta
Journal Volume
411
Journal Issue
19-20
Pages
1428-1431
Date Issued
2010
Author(s)
Dajnoki A.
Fekete G.
Keutzer J.
Orsini J.J.
De Jesus V.R.
Lukacs Z.
M?hl A.
Zhang X.K.
Bodamer O.
Abstract
Background: Fabry 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. Methods: One 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. Results: The 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. 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. ? 2010 Elsevier B.V.
SDGs
Other Subjects
alpha galactosidase; article; blood analysis; controlled study; enzyme activity; Fabry disease; female; human; male; newborn; newborn screening; priority journal; reference value; tandem mass spectrometry; validity; alpha-Galactosidase; Fabry Disease; Female; Humans; Infant, Newborn; Male; Neonatal Screening; Sex Factors; Tandem Mass Spectrometry
Type
journal article