Thomas J Langan1, Joseph J Orsini2, Kabir Jalal3, Amy L Barczykowski3, Maria L Escolar4, Michele D Poe4, Chad K Biski2, Randy L Carter3. 1. Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA. tjlangan@buffalo.edu. 2. Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA. 3. Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA. 4. The Program for the Study of Neurodevelopment in Rare Disorders, Children's Hospital Pittsburgh of UPMC, Pittsburgh, PA, USA.
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.
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: Allison M Bradbury; Jessica H Bagel; Duc Nguyen; Erik A Lykken; Jill Pesayco Salvador; Xuntian Jiang; Gary P Swain; Charles A Assenmacher; Ian J Hendricks; Keiko Miyadera; Rebecka S Hess; Arielle Ostrager; Patricia ODonnell; Mark S Sands; Daniel S Ory; G Diane Shelton; Ernesto R Bongarzone; Steven J Gray; Charles H Vite Journal: J Clin Invest Date: 2020-09-01 Impact factor: 14.808
Authors: Thomas J Langan; Amy Barczykowski; Kabir Jalal; Laura Sherwood; Heather Allewelt; Joanne Kurtzberg; Randy L Carter Journal: JIMD Rep Date: 2019-04-11
Authors: Zackary Herbst; Coleman T Turgeon; Chad Biski; Hamid Khaledi; Nancy B Shoemaker; Patrick D DeArmond; Sara Smith; Joseph Orsini; Dietrich Matern; Michael H Gelb Journal: Int J Neonatal Screen Date: 2020-03-31