Implementation of newborn screening for Krabbe disease: Population study and cutoff determination

Newborn Screening for Hunter Disease: A Small-Scale Feasibility Study

“…Based on this result, the recall rate would be 0.07%. Although this number remains to be confirmed by larger studies, it is comparable to the results obtained in studies for other lysosomal storage disorders: Pompe disease (0.039%) (Dajnoki et al 2008) and Krabbe disease (0.06%) (Orsini et al 2009). A higher recall rate (0.82%) was reported by Chien et al for Pompe NBS in Taiwan, but this likely results from a common a-glucosidase variant with low enzyme activity present in the Asian population (Chien et al 2008).…”

“…Early intervention requires identification of patients at a very early age, before clinical features have become evident, i.e., by newborn screening (NBS) (Marsden and Levy 2010;Zhou et al 2011). NBS has been reported for a number of lysosomal storage disorders including Pompe disease (Chien et al 2008;Dajnoki et al 2008), Fabry disease (Dajnoki et al 2010), and Krabbe disease (Orsini et al 2009), but not for MPS II. Enzymatic assays for measuring the IDS activity in dried blood spots have been described in fluorometric (Oemardien et al 2011;Tolun et al 2012) and in tandem mass spectrometric (Wolfe et al 2011) platforms.…”

Newborn screening for Krabbe disease in New York State: the first eight years’ experience

“…25 Activity (µmol/ hour/l) is converted to percent activity based on the daily mean activity (DMA). Specimens with ≤20% DMA are retested in duplicate using new punches from the original dried blood spots, and specimens with mean GALC ≤12% DMA (initial plus two repeat punches) are subjected to molecular GALC analysis.…”

“…Infants with at least one potentially clinically relevant variant/mutation are considered screen-positive and referred to a NYS-accredited inherited metabolic disease Specialty Care Center for diagnostic testing, genetic counseling, and clinical/ neurological examination. 21 Details regarding GALC enzyme and molecular assays, the diagnostic assay, and follow-up procedures have been published 21,22,25 or are included in Supplementary Methods and Supplementary Tables S1 and S2 online. Specimens collected from infants born during the first 8 years of screening are included in this study (through 7 August 2014).…”

“…25 Missouri has recently begun screening, 26 and several other states have pending mandates to screen KD and/or other LSDs. 16 Here, we describe our two-tiered enzyme and molecular screening assay and provide results from the first 1.9 million infants screened over the course of 8 years.…”