In a recent study, Fanny Thuriot, Université de Sherbrooke and Sherbrooke Genomic Medicine, Sherbrooke, QC, Canada, and colleagues presented data providing support for the reflex use of acid alpha-glucosidase enzymatic assay on dried blood spots following molecular analysis to confirm the diagnosis of Pompe disease in symptomatic patients. Parallel analysis was conducted on 1430 patients, resulting in diagnosis of Pompe disease in 14 (0.69%) patients. Low enzyme activity overlapping that of Pompe disease was identified in 7 additional patients. The authors highlight that reflex enzymatic testing may decrease the risk of a missed diagnosis when one pathogenic variant is detected via DNA sequencing, and may help confirm or rule out Pompe disease in the case of a genotype of uncertain clinical significance.