Umbilical Cord Blood Sampling for Newborn Screening of Pompe Disease and the Detection of a Novel Pathogenic Variant and Pseudodeficiency Variants in an Asian population
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Background: Pompe disease is an autosomal recessive metabolic disorder caused by acid alpha-glucosidase (GAA) deficiency. The use of umbilical cord blood (UCB) for newborn screening (NBS) of Pompe disease, compared to heel-prick sampling, has not been widely studied. Methods: This study compared GAA activity in UCB from term newborns with peripheral or heel-prick blood samples obtained on days 1, 2, and 3 after birth. Enzyme assays were performed using UPLC-MS/MS. Sanger sequencing was conducted in in-fants with low GAA activity to identify pathogenic variants. Results: Among 4,091 UCB samples analyzed over 18 months, mean GAA activity was 10.04 ± 5.95 μM/h, higher in females than males (9.83 ± 5.45 vs. 9.08 ± 4.97 μM/h, p< 0.001), and similar across ethnicities. GAA levels in UCB and Day 3 heel-prick sam-ples were comparable. A GAA cut-off value of 1.54 μM/h (0.1% of study population) identified one infant (0.024% prevalence) with a novel bi-allelic vari-ant—c.2005_2010del (p.Pro669_Phe670del) and c.1123C>T (p.Arg375Cys), and 12 in-fants with non-pathogenic pseudodeficiency alleles. Conclusion: Our study supports GAA measurement in UCB as a viable alterna-tive for NBS, with enzyme activity remaining stable for up to 72-hours post-collection. Larger-scale multicenter nationwide studies are warranted to confirm this prevalence in our population.