Melissa P Wasserstein1, Mary Andriola2, Georgianne Arnold3,4, Alan Aron5,6, Patricia Duffner7, Richard W Erbe8, Maria L Escolar3,4, Lissette Estrella9, Patricia Galvin-Parton10, Alejandro Iglesias11, Denise M Kay12, David F Kronn13, Joanne Kurtzberg14,15, Jennifer M Kwon16,17,18, Thomas J Langan19,20, Paul A Levy21, Thomas P Naidich22,23,5, Joseph J Orsini12, Joan E Pellegrino24, James M Provenzale25, David A Wenger26, Michele Caggana12. 1. Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, USA. 2. Department of Neurology, Stony Brook University School of Medicine, Stony Brook, New York, USA. 3. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 4. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 5. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 6. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 7. Department of Neurology (emeritus), University at Buffalo School of Medicine, Buffalo, New York, USA. 8. Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York, USA. 9. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 10. Department of Pediatrics, Stony Brook University School of Medicine, Stony Brook, New York, USA. 11. Department of Pediatrics, Columbia University Medical Center, New York, New York, USA. 12. Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA. 13. Department of Pediatrics, New York Medical College, Valhalla, New York, USA. 14. Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA. 15. Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA. 16. Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. 17. Department of Pathology, University of Rochester Medical Center, Rochester, New York, USA. 18. Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA. 19. Department of Neurology, University of Buffalo, Buffalo, New York, USA. 20. Hunter James Kelly Research Institute, University of Buffalo, Buffalo, New York, USA. 21. Department of Pediatrics, Children's Hospital at Montefiore, Bronx, New York, USA. 22. Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 23. Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 24. Department of Pediatrics, Upstate Medical University, Syracuse, New York, USA. 25. Department of Radiology, Duke University School of Medicine, Durham, North Carolina, USA. 26. Lysosomal Diseases Testing Laboratory, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Abstract
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.
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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