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 J. Adams, Georgianne L. Arnold, Alejandro Iglesias, Patricia Galvin-Parton, David F. Kronn, Jennifer M. Kwon, Paul A. Levy, Joan E. PellegrinoNatasha Shur, Melissa P. Wasserstein, Michele Caggana

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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
Issue number3
StatePublished - Mar 1 2016


  • GALC gene
  • Krabbe disease newborn screening
  • galactocerebrosidase/galactosylceramidase
  • globoid cell leukodystrophy
  • lysosomal storage disorder

ASJC Scopus subject areas

  • Genetics(clinical)


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