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Genet Med. 2016 Mar;18(3):239-48. doi: 10.1038/gim.2015.211. Epub 2016 Jan 21.

Newborn screening for Krabbe disease in New York State: the first eight years' experience.

Author information

1
Laboratory of Human Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
2
Lysosomal Diseases Testing Laboratory, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
3
Hunter James Kelly Research Institute, University of Buffalo, Buffalo, New York, USA.
4
Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York, USA.
5
Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
6
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
7
Division of Genetics, Department of Pediatrics, Albany Medical Center, Albany, New York, USA.
8
Genetics and Metabolism, Goryeb Children's Hospital, Atlantic Health System, Morristown, New Jersey, USA.
9
Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA.
10
Department of Pediatrics, Columbia University Medicine Center, New York, New York, USA.
11
Department of Pediatrics, University Medical Center at Stony Brook, Stony Brook, New York, USA.
12
Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
13
Department of Pediatrics, Children's Hospital at Montefiore, Bronx, New York, USA.
14
Department of Pediatrics, Upstate Medical University, Syracuse, New York, USA.
15
Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.

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.

PMID:
26795590
DOI:
10.1038/gim.2015.211
[Indexed for MEDLINE]

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