Escolar ML, Kiely BT, Shawgo E, et al.
Psychosine, a marker of Krabbe phenotype and treatment effect. Mol Genet Metab. 2017;121(3):271-278.
Newborn screening (NBS) for Krabbe disease (KD) has recently started in a number of US states. Much of the controversy surrounding NBS for KD has centered on the challenges associated with predicting how the disease will progress (also known as phenotype) and long-term outcomes in patients that are determined to be at risk for KD. This is the first study to assess the clinical value of psychosine as a biomarker (ADD THIS AS A HOVER OVER to biomarker: A biomarker may be a useful tool to help physicians understand disease progression or response to treatment.) based on measurements of dried blood spot (DBS) psychosine levels gathered over a long period of time in a population of untreated and treated patients with Krabbe disease.
- From 2010 to 2016, DBS samples were prospectively collected from 69 patients with a confirmed diagnosis of KD, four sibling carriers, and two asymptomatic NBS-positive patients during clinical evaluations at the Program for the Study of Neurodevelopment in Rare Disorders (NDRD).
- Galactosylsphingosine, also known as psychosine, is a substrate of the GALC enzyme that shows promise to help in the diagnosis and follow-up of at-risk infants identified through NBS.
- Elevated DBS psychosine at birth showed high specificity as a marker for KD.
- Since GALC enzyme activity has not been shown to reliably predict the disease course, these findings support the use of DBS psychosine levels as a second-tier NBS test to help in the identification of patients who require urgent evaluation for hematopoietic stem cell transplantation (HSCT).
- These results indicate that infants that have a NBS-positive result with high DBS psychosine concentrations should be immediately referred for HSCT evaluation.
- In addition, longitudinal assessments showed that both natural disease progression and treatment with HSCT were associated with decreases in DBS psychosine concentrations.
- The authors 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.
Substantially elevated DBS psychosine concentration during the newborn period was found to be a highly specific biomarker for infantile Krabbe disease and may serve useful as a second-tier newborn screening test.