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

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


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