Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders

Victor R. De Jesus, X. Kate Zhang, Joan Keutzer, Olaf A. Bodamer, Adolf Mühl, Joseph J. Orsini, Michele Caggana, Robert F. Vogt, W. Harry Hannon

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Lysosomal storage disorders (LSDs) comprise more than 40 genetic diseases that result in the accumulation of products that would normally be degraded by lysosomal enzymes. A tandem mass spectrometry (MS/MS)-based method is available for newborn screening for 5 LSDs, and many laboratories are initiating pilot studies to evaluate the incorporation of this method into their screening panels. We developed and evaluated dried blood spot (DBS) QC materials for LSDs and used the MS/MS method to investigate their suitability for LSD QC monitoring. METHODS: We incubated 3.2-mm punches from DBS controls for 20-24 h with assay cocktails containing substrate and internal standard. Using MS/MS, we quantified the resulting product and internal standard. Samples were run in triplicate for 3 consecutive days, and results were reported as product-to-internal standard ratios and enzyme activity units (μmol/L/h). RESULTS: Enzyme activity interday imprecision (CV) for the high, medium, and low series were 3.4%-14.3% for galactocerebroside α-galactosidase, 6.8%-24.6% for acid α-galactosidase A, 7.36%-22.1% for acid sphingomyelinase, 6.2%-26.2% for acid α-glucocerebrosidase, and 7.0%-24.8% for lysosomal acid α-glucosidase (n = 9). In addition, DBS stored at -20° and 4°C showed minimal enzyme activity loss over a 187-d period. DBS stored at 37° and 45° C had lower activity values over the 187-day evaluation time. CONCLUSIONS: Suitable QC materials for newborn screening of LSDs were developed for laboratories performing DBS LSD screening. Good material linearity was observed, with goodness-of-fit values of 0.953 and higher. The QC materials may be used by screening laboratories that perform LSD analysis by MS and/or more conventional fluorescence-based screening methods.

Original languageEnglish
Pages (from-to)158-164
Number of pages7
JournalClinical Chemistry
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2009

Fingerprint

Quality Control
Quality control
Screening
Blood
Galactosidases
Enzyme activity
Acids
Enzymes
Glucosylceramidase
Glucosidases
Sphingomyelin Phosphodiesterase
Inborn Genetic Diseases
Tandem Mass Spectrometry
Fluorescence
Mass spectrometry
Assays
Monitoring
Substrates

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

De Jesus, V. R., Zhang, X. K., Keutzer, J., Bodamer, O. A., Mühl, A., Orsini, J. J., ... Hannon, W. H. (2009). Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders. Clinical Chemistry, 55(1), 158-164. https://doi.org/10.1373/clinchem.2008.111864

Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders. / De Jesus, Victor R.; Zhang, X. Kate; Keutzer, Joan; Bodamer, Olaf A.; Mühl, Adolf; Orsini, Joseph J.; Caggana, Michele; Vogt, Robert F.; Hannon, W. Harry.

In: Clinical Chemistry, Vol. 55, No. 1, 01.01.2009, p. 158-164.

Research output: Contribution to journalArticle

De Jesus, VR, Zhang, XK, Keutzer, J, Bodamer, OA, Mühl, A, Orsini, JJ, Caggana, M, Vogt, RF & Hannon, WH 2009, 'Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders', Clinical Chemistry, vol. 55, no. 1, pp. 158-164. https://doi.org/10.1373/clinchem.2008.111864
De Jesus, Victor R. ; Zhang, X. Kate ; Keutzer, Joan ; Bodamer, Olaf A. ; Mühl, Adolf ; Orsini, Joseph J. ; Caggana, Michele ; Vogt, Robert F. ; Hannon, W. Harry. / Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders. In: Clinical Chemistry. 2009 ; Vol. 55, No. 1. pp. 158-164.
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abstract = "BACKGROUND: Lysosomal storage disorders (LSDs) comprise more than 40 genetic diseases that result in the accumulation of products that would normally be degraded by lysosomal enzymes. A tandem mass spectrometry (MS/MS)-based method is available for newborn screening for 5 LSDs, and many laboratories are initiating pilot studies to evaluate the incorporation of this method into their screening panels. We developed and evaluated dried blood spot (DBS) QC materials for LSDs and used the MS/MS method to investigate their suitability for LSD QC monitoring. METHODS: We incubated 3.2-mm punches from DBS controls for 20-24 h with assay cocktails containing substrate and internal standard. Using MS/MS, we quantified the resulting product and internal standard. Samples were run in triplicate for 3 consecutive days, and results were reported as product-to-internal standard ratios and enzyme activity units (μmol/L/h). RESULTS: Enzyme activity interday imprecision (CV) for the high, medium, and low series were 3.4{\%}-14.3{\%} for galactocerebroside α-galactosidase, 6.8{\%}-24.6{\%} for acid α-galactosidase A, 7.36{\%}-22.1{\%} for acid sphingomyelinase, 6.2{\%}-26.2{\%} for acid α-glucocerebrosidase, and 7.0{\%}-24.8{\%} for lysosomal acid α-glucosidase (n = 9). In addition, DBS stored at -20° and 4°C showed minimal enzyme activity loss over a 187-d period. DBS stored at 37° and 45° C had lower activity values over the 187-day evaluation time. CONCLUSIONS: Suitable QC materials for newborn screening of LSDs were developed for laboratories performing DBS LSD screening. Good material linearity was observed, with goodness-of-fit values of 0.953 and higher. The QC materials may be used by screening laboratories that perform LSD analysis by MS and/or more conventional fluorescence-based screening methods.",
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AU - Zhang, X. Kate

AU - Keutzer, Joan

AU - Bodamer, Olaf A.

AU - Mühl, Adolf

AU - Orsini, Joseph J.

AU - Caggana, Michele

AU - Vogt, Robert F.

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N2 - BACKGROUND: Lysosomal storage disorders (LSDs) comprise more than 40 genetic diseases that result in the accumulation of products that would normally be degraded by lysosomal enzymes. A tandem mass spectrometry (MS/MS)-based method is available for newborn screening for 5 LSDs, and many laboratories are initiating pilot studies to evaluate the incorporation of this method into their screening panels. We developed and evaluated dried blood spot (DBS) QC materials for LSDs and used the MS/MS method to investigate their suitability for LSD QC monitoring. METHODS: We incubated 3.2-mm punches from DBS controls for 20-24 h with assay cocktails containing substrate and internal standard. Using MS/MS, we quantified the resulting product and internal standard. Samples were run in triplicate for 3 consecutive days, and results were reported as product-to-internal standard ratios and enzyme activity units (μmol/L/h). RESULTS: Enzyme activity interday imprecision (CV) for the high, medium, and low series were 3.4%-14.3% for galactocerebroside α-galactosidase, 6.8%-24.6% for acid α-galactosidase A, 7.36%-22.1% for acid sphingomyelinase, 6.2%-26.2% for acid α-glucocerebrosidase, and 7.0%-24.8% for lysosomal acid α-glucosidase (n = 9). In addition, DBS stored at -20° and 4°C showed minimal enzyme activity loss over a 187-d period. DBS stored at 37° and 45° C had lower activity values over the 187-day evaluation time. CONCLUSIONS: Suitable QC materials for newborn screening of LSDs were developed for laboratories performing DBS LSD screening. Good material linearity was observed, with goodness-of-fit values of 0.953 and higher. The QC materials may be used by screening laboratories that perform LSD analysis by MS and/or more conventional fluorescence-based screening methods.

AB - BACKGROUND: Lysosomal storage disorders (LSDs) comprise more than 40 genetic diseases that result in the accumulation of products that would normally be degraded by lysosomal enzymes. A tandem mass spectrometry (MS/MS)-based method is available for newborn screening for 5 LSDs, and many laboratories are initiating pilot studies to evaluate the incorporation of this method into their screening panels. We developed and evaluated dried blood spot (DBS) QC materials for LSDs and used the MS/MS method to investigate their suitability for LSD QC monitoring. METHODS: We incubated 3.2-mm punches from DBS controls for 20-24 h with assay cocktails containing substrate and internal standard. Using MS/MS, we quantified the resulting product and internal standard. Samples were run in triplicate for 3 consecutive days, and results were reported as product-to-internal standard ratios and enzyme activity units (μmol/L/h). RESULTS: Enzyme activity interday imprecision (CV) for the high, medium, and low series were 3.4%-14.3% for galactocerebroside α-galactosidase, 6.8%-24.6% for acid α-galactosidase A, 7.36%-22.1% for acid sphingomyelinase, 6.2%-26.2% for acid α-glucocerebrosidase, and 7.0%-24.8% for lysosomal acid α-glucosidase (n = 9). In addition, DBS stored at -20° and 4°C showed minimal enzyme activity loss over a 187-d period. DBS stored at 37° and 45° C had lower activity values over the 187-day evaluation time. CONCLUSIONS: Suitable QC materials for newborn screening of LSDs were developed for laboratories performing DBS LSD screening. Good material linearity was observed, with goodness-of-fit values of 0.953 and higher. The QC materials may be used by screening laboratories that perform LSD analysis by MS and/or more conventional fluorescence-based screening methods.

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