Newborn screening for Krabbe disease in New York State

The first eight years' experience

Joseph J. Orsini, Denise M. Kay, Carlos A. Saavedra-Matiz, David A. Wenger, Patricia K. Duffner, Richard W. Erbe, Chad Biski, Monica Martin, Lea M. Krein, Matthew Nichols, Joanne Kurtzberg, Maria L. Escolar, Darius Adams, Georgianne L. Arnold, Alejandro Iglesias, Patricia Galvin-Parton, David F. Kronn, Jennifer M. Kwon, Paul A. Levy, Joan E. Pellegrino & 3 others Natasha Shur, Melissa P. Wasserstein, Michele Caggana

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Purpose:Krabbe disease (KD) results from galactocerebrosidase (GALC) deficiency. Infantile KD symptoms include irritability, progressive stiffness, developmental delay, and death. The only potential treatment is hematopoietic stem cell transplantation. New York State (NYS) implemented newborn screening for KD in 2006.Methods:Dried blood spots from newborns were assayed for GALC enzyme activity using mass spectrometry, followed by molecular analysis for those with low activity (≤12% of the daily mean). Infants with low enzyme activity and one or more mutations were referred for follow-up diagnostic testing and neurological examination.Results:Of >1.9 million screened, 620 infants were subjected to molecular analysis and 348 were referred for diagnostic testing. Five had enzyme activities and mutations consistent with infantile KD and manifested clinical/neurodiagnostic abnormalities. Four underwent transplantation, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. The significance of many sequence variants identified is unknown. Forty-six asymptomatic infants were found to be at moderate to high risk for disease.Conclusions:The positive predictive value of KD screening in NYS is 1.4% (5/346) considering confirmed infantile cases. The incidence of infantile KD in NYS is approximately 1 in 394,000, but it may be higher for later-onset forms.

Original languageEnglish (US)
Pages (from-to)239-248
Number of pages10
JournalGenetics in Medicine
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2016

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Globoid Cell Leukodystrophy
Newborn Infant
Dried Blood Spot Testing
Galactosylceramidase
Enzymes
Mutation
Hematopoietic Stem Cell Transplantation
Neurologic Examination
Mass Spectrometry
Transplantation
Transplants
Incidence

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

Orsini, J. J., Kay, D. M., Saavedra-Matiz, C. A., Wenger, D. A., Duffner, P. K., Erbe, R. W., ... Caggana, M. (2016). Newborn screening for Krabbe disease in New York State: The first eight years' experience. Genetics in Medicine, 18(3), 239-248. https://doi.org/10.1038/gim.2015.211
Orsini, Joseph J. ; Kay, Denise M. ; Saavedra-Matiz, Carlos A. ; Wenger, David A. ; Duffner, Patricia K. ; Erbe, Richard W. ; Biski, Chad ; Martin, Monica ; Krein, Lea M. ; Nichols, Matthew ; Kurtzberg, Joanne ; Escolar, Maria L. ; Adams, Darius ; Arnold, Georgianne L. ; Iglesias, Alejandro ; Galvin-Parton, Patricia ; Kronn, David F. ; Kwon, Jennifer M. ; Levy, Paul A. ; Pellegrino, Joan E. ; Shur, Natasha ; Wasserstein, Melissa P. ; Caggana, Michele. / Newborn screening for Krabbe disease in New York State : The first eight years' experience. In: Genetics in Medicine. 2016 ; Vol. 18, No. 3. pp. 239-248.
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abstract = "Purpose:Krabbe disease (KD) results from galactocerebrosidase (GALC) deficiency. Infantile KD symptoms include irritability, progressive stiffness, developmental delay, and death. The only potential treatment is hematopoietic stem cell transplantation. New York State (NYS) implemented newborn screening for KD in 2006.Methods:Dried blood spots from newborns were assayed for GALC enzyme activity using mass spectrometry, followed by molecular analysis for those with low activity (≤12{\%} of the daily mean). Infants with low enzyme activity and one or more mutations were referred for follow-up diagnostic testing and neurological examination.Results:Of >1.9 million screened, 620 infants were subjected to molecular analysis and 348 were referred for diagnostic testing. Five had enzyme activities and mutations consistent with infantile KD and manifested clinical/neurodiagnostic abnormalities. Four underwent transplantation, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. The significance of many sequence variants identified is unknown. Forty-six asymptomatic infants were found to be at moderate to high risk for disease.Conclusions:The positive predictive value of KD screening in NYS is 1.4{\%} (5/346) considering confirmed infantile cases. The incidence of infantile KD in NYS is approximately 1 in 394,000, but it may be higher for later-onset forms.",
author = "Orsini, {Joseph J.} and Kay, {Denise M.} and Saavedra-Matiz, {Carlos A.} and Wenger, {David A.} and Duffner, {Patricia K.} and Erbe, {Richard W.} and Chad Biski and Monica Martin and Krein, {Lea M.} and Matthew Nichols and Joanne Kurtzberg and Escolar, {Maria L.} and Darius Adams and Arnold, {Georgianne L.} and Alejandro Iglesias and Patricia Galvin-Parton and Kronn, {David F.} and Kwon, {Jennifer M.} and Levy, {Paul A.} and Pellegrino, {Joan E.} and Natasha Shur and Wasserstein, {Melissa P.} and Michele Caggana",
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Orsini, JJ, Kay, DM, Saavedra-Matiz, CA, Wenger, DA, Duffner, PK, Erbe, RW, Biski, C, Martin, M, Krein, LM, Nichols, M, Kurtzberg, J, Escolar, ML, Adams, D, Arnold, GL, Iglesias, A, Galvin-Parton, P, Kronn, DF, Kwon, JM, Levy, PA, Pellegrino, JE, Shur, N, Wasserstein, MP & Caggana, M 2016, 'Newborn screening for Krabbe disease in New York State: The first eight years' experience', Genetics in Medicine, vol. 18, no. 3, pp. 239-248. https://doi.org/10.1038/gim.2015.211

Newborn screening for Krabbe disease in New York State : The first eight years' experience. / Orsini, Joseph J.; Kay, Denise M.; Saavedra-Matiz, Carlos A.; Wenger, David A.; Duffner, Patricia K.; Erbe, Richard W.; Biski, Chad; Martin, Monica; Krein, Lea M.; Nichols, Matthew; Kurtzberg, Joanne; Escolar, Maria L.; Adams, Darius; Arnold, Georgianne L.; Iglesias, Alejandro; Galvin-Parton, Patricia; Kronn, David F.; Kwon, Jennifer M.; Levy, Paul A.; Pellegrino, Joan E.; Shur, Natasha; Wasserstein, Melissa P.; Caggana, Michele.

In: Genetics in Medicine, Vol. 18, No. 3, 01.03.2016, p. 239-248.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Newborn screening for Krabbe disease in New York State

T2 - The first eight years' experience

AU - Orsini, Joseph J.

AU - Kay, Denise M.

AU - Saavedra-Matiz, Carlos A.

AU - Wenger, David A.

AU - Duffner, Patricia K.

AU - Erbe, Richard W.

AU - Biski, Chad

AU - Martin, Monica

AU - Krein, Lea M.

AU - Nichols, Matthew

AU - Kurtzberg, Joanne

AU - Escolar, Maria L.

AU - Adams, Darius

AU - Arnold, Georgianne L.

AU - Iglesias, Alejandro

AU - Galvin-Parton, Patricia

AU - Kronn, David F.

AU - Kwon, Jennifer M.

AU - Levy, Paul A.

AU - Pellegrino, Joan E.

AU - Shur, Natasha

AU - Wasserstein, Melissa P.

AU - Caggana, Michele

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Purpose:Krabbe disease (KD) results from galactocerebrosidase (GALC) deficiency. Infantile KD symptoms include irritability, progressive stiffness, developmental delay, and death. The only potential treatment is hematopoietic stem cell transplantation. New York State (NYS) implemented newborn screening for KD in 2006.Methods:Dried blood spots from newborns were assayed for GALC enzyme activity using mass spectrometry, followed by molecular analysis for those with low activity (≤12% of the daily mean). Infants with low enzyme activity and one or more mutations were referred for follow-up diagnostic testing and neurological examination.Results:Of >1.9 million screened, 620 infants were subjected to molecular analysis and 348 were referred for diagnostic testing. Five had enzyme activities and mutations consistent with infantile KD and manifested clinical/neurodiagnostic abnormalities. Four underwent transplantation, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. The significance of many sequence variants identified is unknown. Forty-six asymptomatic infants were found to be at moderate to high risk for disease.Conclusions:The positive predictive value of KD screening in NYS is 1.4% (5/346) considering confirmed infantile cases. The incidence of infantile KD in NYS is approximately 1 in 394,000, but it may be higher for later-onset forms.

AB - Purpose:Krabbe disease (KD) results from galactocerebrosidase (GALC) deficiency. Infantile KD symptoms include irritability, progressive stiffness, developmental delay, and death. The only potential treatment is hematopoietic stem cell transplantation. New York State (NYS) implemented newborn screening for KD in 2006.Methods:Dried blood spots from newborns were assayed for GALC enzyme activity using mass spectrometry, followed by molecular analysis for those with low activity (≤12% of the daily mean). Infants with low enzyme activity and one or more mutations were referred for follow-up diagnostic testing and neurological examination.Results:Of >1.9 million screened, 620 infants were subjected to molecular analysis and 348 were referred for diagnostic testing. Five had enzyme activities and mutations consistent with infantile KD and manifested clinical/neurodiagnostic abnormalities. Four underwent transplantation, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. The significance of many sequence variants identified is unknown. Forty-six asymptomatic infants were found to be at moderate to high risk for disease.Conclusions:The positive predictive value of KD screening in NYS is 1.4% (5/346) considering confirmed infantile cases. The incidence of infantile KD in NYS is approximately 1 in 394,000, but it may be higher for later-onset forms.

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Orsini JJ, Kay DM, Saavedra-Matiz CA, Wenger DA, Duffner PK, Erbe RW et al. Newborn screening for Krabbe disease in New York State: The first eight years' experience. Genetics in Medicine. 2016 Mar 1;18(3):239-248. https://doi.org/10.1038/gim.2015.211