Browsing by Author "Erbe, Richard W"

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    Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State.
    (Genetics in medicine : official journal of the American College of Medical Genetics, 2016-12) Wasserstein, Melissa P; Andriola, Mary; Arnold, Georgianne; Aron, Alan; Duffner, Patricia; Erbe, Richard W; Escolar, Maria L; Estrella, Lissette; Galvin-Parton, Patricia; Iglesias, Alejandro; Kay, Denise M; Kronn, David F; Kurtzberg, Joanne; Kwon, Jennifer M; Langan, Thomas J; Levy, Paul A; Naidich, Thomas P; Orsini, Joseph J; Pellegrino, Joan E; Provenzale, James M; Wenger, David A; Caggana, Michele

    Background

    Early infantile Krabbe disease is rapidly fatal, but hematopoietic stem cell transplantation (HSCT) may improve outcomes if performed soon after birth. New York State began screening all newborns for Krabbe disease in 2006.

    Methods

    Infants with abnormal newborn screen results for Krabbe disease were referred to specialty-care centers. Newborns found to be at high risk for Krabbe disease underwent a neurodiagnostic battery to determine the need for emergent HSCT.

    Results

    Almost 2 million infants were screened. Five infants were diagnosed with early infantile Krabbe disease. Three died, two from HSCT-related complications and one from untreated disease. Two children who received HSCT have moderate to severe developmental delays. Forty-six currently asymptomatic children are considered to be at moderate or high risk for development of later-onset Krabbe disease.

    Conclusions

    These results show significant HSCT-associated morbidity and mortality in early infantile Krabbe disease and raise questions about its efficacy when performed in newborns diagnosed through newborn screening. The unanticipated identification of "at risk" children introduces unique ethical and medicolegal issues. New York's experience raises questions about the risks, benefits, and practicality of screening newborns for Krabbe disease. It is imperative that objective assessments be made on an ongoing basis as additional states begin screening for this disorder.Genet Med 18 12, 1235-1243.
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    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, 2016-03) Orsini, Joseph J; Kay, Denise M; Saavedra-Matiz, Carlos A; Wenger, David A; Duffner, Patricia K; Erbe, Richard W; Biski, Chad; Martin, Monica; Krein, Lea M; Nichols, Matthew; Kurtzberg, Joanne; Escolar, Maria L; Adams, Darius J; Arnold, Georgianne L; Iglesias, Alejandro; Galvin-Parton, Patricia; Kronn, David F; Kwon, Jennifer M; Levy, Paul A; Pellegrino, Joan E; Shur, Natasha; Wasserstein, Melissa P; Caggana, Michele; New York State Krabbe Disease Consortium

    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.