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



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.


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.


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).


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.

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Fig. 1: Psychosine concentration and GALC activity in different patient groups.
Fig. 2: Individual patient results in relation to control and patient populations.
Fig. 3: Psychosine concentration over time.
Fig. 4: Algorithm for follow up of an abnormal newborn screen for Krabbe disease based on galactocerebrosidase (GALC) activity as 1st tier test and psychosine (PSY) concentration as 2nd tier test.


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Correspondence to Dietrich Matern MD, PhD.

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Guenzel, A.J., Turgeon, C.T., Nickander, K.K. et al. The critical role of psychosine in screening, diagnosis, and monitoring of Krabbe disease. Genet Med 22, 1108–1118 (2020).

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

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