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

Abstract

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.

• 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
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 411 Issue 19-20 Pg. 1428-31 (Oct 09 2010) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 20338160 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• alpha-Galactosidase

Topics

• Fabry Disease (diagnosis)
• Female
• Humans
• Infant, Newborn
• Male
• Neonatal Screening (methods)
• Sex Factors
• Tandem Mass Spectrometry (methods)
• alpha-Galactosidase (blood, metabolism)