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Mol Genet Metab. 2017 Jul;121(3):271-278. doi: 10.1016/j.ymgme.2017.05.015. Epub 2017 May 22.

Psychosine, a marker of Krabbe phenotype and treatment effect.

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Program for the Study of Neurodevelopment in Rare Disorders, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA. Electronic address:
Program for the Study of Neurodevelopment in Rare Disorders, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA 98195, USA.
Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.


Newborn screening (NBS) for Krabbe disease, a rare neurodegenerative disorder caused by deficient galactocerebrosidase (GALC) enzyme activity, has recently been implemented in a number of US states. However, the spectrum of phenotypic manifestations associated with deficient GALC activity complicates the management of screen-positive newborns and underscores the need to identify clinically relevant biomarkers. Earlier studies with a small number of patients identified psychosine, a substrate of the GALC enzyme, as a potential biomarker for Krabbe disease. In this study, we provide, for the first time, longitudinal data on dried blood spot (DBS) psychosine concentrations in different Krabbe disease phenotypes for both untreated patients and those treated with hematopoietic stem cell transplantation (HSCT). Our cohort included patients previously identified by NBS to be at high risk to develop Krabbe disease. Substantially elevated DBS psychosine concentration during the newborn period was found to be a highly specific marker for infantile Krabbe disease. This finding supports the use of DBS psychosine concentration as a second-tier NBS test to aid in the identification of patients who require urgent evaluation for HSCT. In addition, longitudinal assessments showed that both natural disease progression and treatment with HSCT were associated with decreases in DBS psychosine concentrations. Based on these findings we provide recommendations for the interpretation of psychosine concentrations in DBS specimens collected during the first year of life. Future studies should aim to better delineate the relationship between DBS psychosine concentration and disease onset in patients with later-onset forms of Krabbe disease.


Galactosylsphingosine; Globoid cell leukodystrophy; Krabbe disease; Newborn screening; Psychosine; Tandem mass spectrometry

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