Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe Disease

Robert Thompson-Stone; Margie A Ream; Michael Gelb; Dietrich Matern; Joseph J Orsini; Paul A Levy; Jennifer P Rubin; David A Wenger; Barbara K Burton; Maria L Escolar; Joanne Kurtzberg

doi:10.1016/j.ymgme.2021.03.016

Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe Disease

Mol Genet Metab. 2021 Sep-Oct;134(1-2):53-59. doi: 10.1016/j.ymgme.2021.03.016. Epub 2021 Apr 3.

Authors

Affiliations

¹ University of Rochester, Golisano Children's Hospital, 601 Elmwood Ave, Rochester, NY 14642, USA. Electronic address: Robert_stone@urmc.rochester.edu.
² Nationwide Children's Hospital Division of Neurology, 700 Children's Dr., Columbus, OH 43205, USA.
³ Departments of Chemistry and Biochemistry, University of Washington, Campus Box 351700, 36 Bagley Hall, Seattle, WA 98195, USA.
⁴ Biochemical Genetics Laboratory, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
⁵ Laboratory of Human Genetics, Wadsworth Center, New York State Dept. of Health, Albany, NY, USA.
⁶ Children's Hospital at Montefiore, Einstein-Montefiore, Pediatric Genetic Medicine, 3411 Wayne Avenue, 9(th) Floor, Bronx, NY 10467, USA.
⁷ Department of Pediatric Neurology, Northwestern Feinberg School of Medicine, 225 E. Chicago Ave, Chicago, IL 60611, USA.
⁸ Department of Neurology, Sidney Kimmel College of Medicine, Thomas Jefferson University, 1020 Locust St, Room 346, Philadelphia, PA 19107, USA.
⁹ Ann & Robert H. Lurie Children's Hospital of Chicago and the Feinberg School of Medicine of Northwestern University, 225 E. Chicago Ave, Chicago, IL 60611, USA.
¹⁰ Department of Pediatrics, University of Pittsburgh Medical Center, Plaza Suite 407, 4401 Penn Ave, Pittsburgh, PA 15224, USA.
¹¹ Marcus Center for Cellular Cures, Duke University School of Medicine, 2400 Pratt Street, Room 9026, Durham, NC 27705, USA.

PMID: 33832819
DOI: 10.1016/j.ymgme.2021.03.016

Abstract

Objective: To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD).

Methods: KD experts (KD NBS Council) met between July 2017 and June 2020 to develop consensus-based classification and follow-up recommendations. The resulting newly proposed recommendations were assessed in a historical cohort of 47 newborns from New York State who were originally classified at moderate or high risk for LOKD.

Results: Infants identified by newborn screening with possible KD should enter one of three clinical follow-up pathways (Early infantile KD, at-risk for LOKD, or unaffected), based on galactocerebrosidase (GALC) activity, psychosine concentration, and GALC genotype. Patients considered at-risk for LOKD based on low GALC activity and an intermediate psychosine concentration are further split into a high-risk or low-risk follow-up pathway based on genotype. Review of the historical New York State cohort found that the updated follow-up recommendations would reduce follow up testing by 88%.

Conclusion: The KD NBS Council has presented updated consensus recommendations for efficient and effective classification and follow-up of NBS positive patients with a focus on long-term follow-up of those at-risk for LOKD.

Keywords: Follow-up; Galactocerebrosidase; Krabbe Disease; Newborn screening; Psychosine.

MeSH terms

Consensus*
Dried Blood Spot Testing
Follow-Up Studies
Genotype*
Humans
Infant
Infant, Newborn
Late Onset Disorders / diagnosis
Late Onset Disorders / etiology
Late Onset Disorders / genetics
Leukodystrophy, Globoid Cell / classification*
Leukodystrophy, Globoid Cell / diagnosis
Leukodystrophy, Globoid Cell / genetics*
Neonatal Screening / methods*
Practice Guidelines as Topic*
Risk Factors