Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry

作者：Dajnoki Angela; Fekete Gyoergy; Keutzer Joan; Orsini Joseph J; De Jesus Victor R; Chien Yin Hsiu; Hwu Wuh Liang; Lukacs Zoltan; Muehl Adolf; Zhang X Kate; Bodamer Olaf^*

来源：Clinica Chimica Acta, 2010, 411(19-20): 1428-1431.

DOI：10.1016/j.cca.2010.03.009

• Fabry disease
• Galactosidase
• Newborn screening
• Dried blood
• Tandem mass spectrometry

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 3.2 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 mu mol/h/l (Cl 95% is 9.67-10.02 mu mol/h/l); The median GLA activity of female newborns (N=4677) was 10.2 +/- 6.3 mu mol/h/l (Cl 95% is 10.02-10.38 mu mol/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 mu mol/h/l. The GLA activities from 32 juvenile and adult females with confirmed FD were below 4.73 mu mol/h/l. In 5 (16%) females GLA activities were above the 0.5th percentile of lower limit of Cl 95% at 3.18 mu mol/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.

• 出版日期2010-10-9