title: Newborn screening for Krabbe disease in New York State: the first eight years' experience.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Orsini
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Denise M
authors.identifier: http://orcid.org/0000-0002-9928-2698
authors.initials: DM
authors.lastname: Kay
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Saavedra-Matiz
authors.affiliation: Lysosomal Diseases Testing Laboratory, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wenger
authors.affiliation: Hunter James Kelly Research Institute, University of Buffalo, Buffalo, New York, USA.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Duffner
authors.affiliation: Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Erbe
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Chad
authors.identifier: http://orcid.org/0000-0002-2075-1528
authors.initials: C
authors.lastname: Biski
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Monica
authors.identifier: http://orcid.org/0000-0002-7850-4941
authors.initials: M
authors.lastname: Martin
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Krein
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Nichols
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Escolar
authors.affiliation: Division of Genetics, Department of Pediatrics, Albany Medical Center, Albany, New York, USA.|Genetics and Metabolism, Goryeb Children's Hospital, Atlantic Health System, Morristown, New Jersey, USA.
authors.forename: Darius J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.|Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Georgianne L
authors.initials: GL
authors.lastname: Arnold
authors.affiliation: Department of Pediatrics, Columbia University Medicine Center, New York, New York, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Department of Pediatrics, University Medical Center at Stony Brook, Stony Brook, New York, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Galvin-Parton
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Kronn
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Jennifer M
authors.identifier: http://orcid.org/0000-0002-7720-2490
authors.initials: JM
authors.lastname: Kwon
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Bronx, New York, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Levy
authors.affiliation: Department of Pediatrics, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Pellegrino
authors.affiliation: Division of Genetics, Department of Pediatrics, Albany Medical Center, Albany, New York, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Shur
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Wasserstein
authors.affiliation: Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
mesh_terms: D000465:Algorithms; D059788:Dried Blood Spot Testing; D005698:Galactosylceramidase / Q000235:genetics* / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007231:Infant, Newborn; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy; D013058:Mass Spectrometry; D015997:Neonatal Screening / Q000379:methods*; D009518:New York; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D005698:Galactosylceramidase