1. Newborn screening for Krabbe disease in New York State: the first eight years' experience
- Author
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Patricia Galvin-Parton, David A. Wenger, Melissa P. Wasserstein, Denise M. Kay, Joan E. Pellegrino, Lea M. Krein, David Kronn, Carlos A. Saavedra-Matiz, Michele Caggana, Richard W. Erbe, Jennifer M. Kwon, Maria L. Escolar, Alejandro D. Iglesias, Chad K. Biski, Natasha Shur, Monica Martin, Georgianne L. Arnold, Joseph J. Orsini, Paul A. Levy, Matthew Nichols, Joanne Kurtzberg, Darius J. Adams, and Patricia K. Duffner
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,medicine.medical_treatment ,New York ,Neurological examination ,Hematopoietic stem cell transplantation ,Asymptomatic ,Polymorphism, Single Nucleotide ,Mass Spectrometry ,03 medical and health sciences ,0302 clinical medicine ,Neonatal Screening ,Predictive Value of Tests ,Medicine ,Humans ,Genetics (clinical) ,Newborn screening ,medicine.diagnostic_test ,business.industry ,Leukodystrophy ,Hematopoietic Stem Cell Transplantation ,Infant, Newborn ,medicine.disease ,Leukodystrophy, Globoid Cell ,Transplantation ,030104 developmental biology ,Treatment Outcome ,Predictive value of tests ,Krabbe disease ,Dried Blood Spot Testing ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Algorithms ,Galactosylceramidase - Abstract
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. 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. 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. 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. Genet Med 18 3, 239–248.
- Published
- 2015