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

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

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1428-1431
Number of pages4
JournalClinica Chimica Acta
Issue number19-20
StatePublished - Oct 2010


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

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical


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