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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1038/gim.2015.211

Publication Info

Orsini, Joseph J, Denise M Kay, Carlos A Saavedra-Matiz, David A Wenger, Patricia K Duffner, Richard W Erbe, Chad Biski, Monica Martin, et al. (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.

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