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.
| Original language | English |
|---|---|
| Pages (from-to) | 1428-1431 |
| Number of pages | 4 |
| Journal | Clinica Chimica Acta |
| Volume | 411 |
| Issue number | 19-20 |
| DOIs | |
| State | Published - Oct 1 2010 |
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Keywords
- Dried blood
- Fabry disease
- Galactosidase
- Newborn screening
- Tandem mass spectrometry
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Biochemistry, medical
Cite this
Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry. / Dajnoki, Angéla; Fekete, György; Keutzer, Joan; Orsini, Joseph J.; De Jesus, Victor R.; Chien, Yin Hsiu; Hwu, Wuh Liang; Lukacs, Zoltan; Mühl, Adolf; Zhang, X. Kate; Bodamer, Olaf.
In: Clinica Chimica Acta, Vol. 411, No. 19-20, 01.10.2010, p. 1428-1431.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry
AU - Dajnoki, Angéla
AU - Fekete, György
AU - Keutzer, Joan
AU - Orsini, Joseph J.
AU - De Jesus, Victor R.
AU - Chien, Yin Hsiu
AU - Hwu, Wuh Liang
AU - Lukacs, Zoltan
AU - Mühl, Adolf
AU - Zhang, X. Kate
AU - Bodamer, Olaf
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
KW - Dried blood
KW - Fabry disease
KW - Galactosidase
KW - Newborn screening
KW - Tandem mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=77955056761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955056761&partnerID=8YFLogxK
U2 - 10.1016/j.cca.2010.03.009
DO - 10.1016/j.cca.2010.03.009
M3 - Article
C2 - 20338160
AN - SCOPUS:77955056761
VL - 411
SP - 1428
EP - 1431
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
IS - 19-20
ER -