The critical role of psychosine in screening, diagnosis, and monitoring of Krabbe disease

Adam J. Guenzel, Coleman T. Turgeon, Kim K. Nickander, Amy L. White, Dawn S. Peck, Gisele B. Pino, April L. Studinski, Vinod K. Prasad, Joanne Kurtzberg, Maria L. Escolar, Maria Laura Duque Lasio, Joan E. Pellegrino, Ai Sakonju, Rachel E. Hickey, Natalie M. Shallow, Margie A. Ream, Joseph J. Orsini, Michael H. Gelb, Kimiyo Raymond, Dimitar K. GavrilovDevin Oglesbee, Piero Rinaldo, Silvia Tortorelli, Dietrich Matern

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Purpose: Newborn screening (NBS) for Krabbe disease (KD) is performed by measurement of galactocerebrosidase (GALC) activity as the primary test. This revealed that GALC activity has poor specificity for KD. Psychosine (PSY) was proposed as a disease marker useful to reduce the false positive rate for NBS and for disease monitoring. We report a highly sensitive PSY assay that allows identification of KD patients with minimal PSY elevations. Methods: PSY was extracted from dried blood spots or erythrocytes with methanol containing d5-PSY as internal standard, and measured by liquid chromatography–tandem mass spectrometry. Results: Analysis of PSY in samples from controls (N = 209), GALC pseudodeficiency carriers (N = 55), GALC pathogenic variant carriers (N = 27), patients with infantile KD (N = 26), and patients with late-onset KD (N = 11) allowed for the development of an effective laboratory screening and diagnostic algorithm. Additional longitudinal measurements were used to track therapeutic efficacy of hematopoietic stem cell transplantion (HSCT). Conclusion: This study supports PSY quantitation as a critical component of NBS for KD. It helps to differentiate infantile from later onset KD variants, as well as from GALC variant and pseudodeficiency carriers. Additionally, this study provides further data that PSY measurement can be useful to monitor KD progression before and after treatment.

Original languageEnglish (US)
Pages (from-to)1108-1118
Number of pages11
JournalGenetics in Medicine
Issue number6
StatePublished - Jun 1 2020


  • Krabbe disease
  • biomarker
  • dried blood spot
  • newborn screening
  • psychosine

ASJC Scopus subject areas

  • Genetics(clinical)


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