Newborn screening for Krabbe disease in New York State: the first eight years' experience.
Abstract
<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Type
Journal articleSubject
New York State Krabbe Disease ConsortiumHumans
Leukodystrophy, Globoid Cell
Galactosylceramidase
Neonatal Screening
Treatment Outcome
Hematopoietic Stem Cell Transplantation
Predictive Value of Tests
Polymorphism, Single Nucleotide
Algorithms
Infant, Newborn
New York
Mass Spectrometry
Dried Blood Spot Testing
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https://hdl.handle.net/10161/24634Published Version (Please cite this version)
10.1038/gim.2015.211Publication Info
Orsini, Joseph J; Kay, Denise M; Saavedra-Matiz, Carlos A; Wenger, David A; Duffner,
Patricia K; Erbe, Richard W; ... New York State Krabbe Disease Consortium (2016). Newborn screening for Krabbe disease in New York State: the first eight years' experience.
Genetics in medicine : official journal of the American College of Medical Genetics, 18(3). pp. 239-248. 10.1038/gim.2015.211. Retrieved from https://hdl.handle.net/10161/24634.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina

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