Development of a newborn screening tool based on bivariate normal limits: using psychosine and galactocerebrosidase determination on dried blood spots to predict Krabbe disease.

Abstract

PURPOSE:

Newborn screening for Krabbe disease (KD) originated in New York State in 2006 but has proven to have a high false positive rate and low positive predictive value. To improve accuracy of presymptomatic prediction, we propose a screening tool based on two biomarkers, psychosine and galactocerebrosidase enzyme activity (GalC).

METHODS:

We developed the tool using measures from dried blood spots of 166 normal newborns and tested it on dried blood spot measures from 15 newborns who later developed KD, 8 newborns identified as "high risk" by the New York screening protocol but were disease-free at follow-up, and 3 symptomatic children with onset before 4 years of age. The tool was developed from the (1-10-6)100% prediction region of the natural logarithms of psychosine and GalC measures, assuming bivariate normality, and their univariate normal limits.

RESULTS:

Krabbe disease was predicted correctly for every patient who developed symptoms in infancy or early childhood. None of the high-risk patients were incorrectly identified as having early KD.

CONCLUSION:

Bivariate analysis of psychosine and GalC in newborn blood spots can accurately predict early Krabbe symptoms, control false positive rates, and permit presymptomatic treatment.

• Authors: Thomas J Langan, Joseph J Orsini, Kabir Jalal, Amy L Barczykowski, Maria L Escolar, Michele D Poe, Chad K Biski, Randy L Carter
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 21 Issue 7 Pg. 1644-1651 (07 2019) ISSN: 1530-0366 [Electronic] United States
• PMID: 30546085 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Validation Study)

Chemical References

• Biomarkers
• Psychosine
• Galactosylceramidase

Topics

• Adult
• Biomarkers (blood)
• Child
• Child, Preschool
• Dried Blood Spot Testing
• Galactosylceramidase (blood)
• Humans
• Infant
• Infant, Newborn
• Leukodystrophy, Globoid Cell (blood, diagnosis)
• Psychosine (blood)