TY - JOUR
T1 - Newborn screening for Krabbe disease in New York State
T2 - The first eight years' experience
AU - Orsini, Joseph J.
AU - Kay, Denise M.
AU - Saavedra-Matiz, Carlos A.
AU - Wenger, David A.
AU - Duffner, Patricia K.
AU - Erbe, Richard W.
AU - Biski, Chad
AU - Martin, Monica
AU - Krein, Lea M.
AU - Nichols, Matthew
AU - Kurtzberg, Joanne
AU - Escolar, Maria L.
AU - Adams, Darius J.
AU - Arnold, Georgianne L.
AU - Iglesias, Alejandro
AU - Galvin-Parton, Patricia
AU - Kronn, David F.
AU - Kwon, Jennifer M.
AU - Levy, Paul A.
AU - Pellegrino, Joan E.
AU - Shur, Natasha
AU - Wasserstein, Melissa P.
AU - Caggana, Michele
N1 - Publisher Copyright:
© American College of Medical Genetics and Genomics.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - GALC gene
KW - Krabbe disease newborn screening
KW - galactocerebrosidase/galactosylceramidase
KW - globoid cell leukodystrophy
KW - lysosomal storage disorder
UR - https://www.scopus.com/pages/publications/84959289821
U2 - 10.1038/gim.2015.211
DO - 10.1038/gim.2015.211
M3 - Article
C2 - 26795590
AN - SCOPUS:84959289821
SN - 1098-3600
VL - 18
SP - 239
EP - 248
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 3
ER -