Algorithm for Pompe disease newborn screening: Results from the Taiwan screening program
Journal
Molecular Genetics and Metabolism
Journal Volume
106
Journal Issue
3
Pages
281-286
Date Issued
2012
Author(s)
Abstract
Background: Pompe disease is caused by a deficiency in acid α-glucosidase (GAA) and results in progressive, debilitating, and often life-threatening symptoms. Newborn screening has led to the early diagnosis of Pompe disease, but the best algorithm for screening has not yet been established. Materials and methods: GAA and neutral α-glucosidase (NAG) activities in dried blood spots (DBSs) were assayed using 4-methylumbelliferyl-β- d-glucopyranoside as the substrate. We also measure α-galactosidase A (GLA) activity in DBSs for comparison. A total of 473,738 newborns were screened for Pompe disease, and the data were analyzed retrospectively to determine the best screening algorithm. Results: The fluorescence assay used in the screening possessed good reproducibility, but the NAG/GAA ratio was superior in separating the true-positive from the false-positive cases. An NAG/GAA cutoff ratio ? 60 produces a positive predictive value (PPV) of 63.4%, and in our sample, only two cases of later-onset Pompe disease would have been missed. The GLA/GAA ratio is not as effective as the NAG/GAA ratio. Conclusion: A suitable control enzyme can improve the performance of newborn screening. Newborn screening for Pompe disease can be performed using the NAG/GAA ratio as a cutoff even in the presence of GAA partial deficiency. ? 2012 Elsevier Inc.
SDGs
Other Subjects
alpha galactosidase; C reactive protein; glucan 1,4 alpha glucosidase; hymecromone glucuronide; I kappa B; accuracy; algorithm; article; clinical article; controlled study; dried blood spot testing; enzyme activity; Fabry disease; false negative result; false positive result; fluorescence; gene expression; gene frequency; gestational age; glycogen storage disease type 2; health program; human; leukocyte; newborn; newborn screening; priority journal; reproducibility; retrospective study; Taiwan; upregulation; Algorithms; alpha-Galactosidase; alpha-Glucosidases; Base Sequence; Glucosides; Glycogen Storage Disease Type II; Humans; Hymecromone; Infant, Newborn; Molecular Sequence Data; Neonatal Screening; Reproducibility of Results; Taiwan
Type
journal article