Newborn screening (NBS) for Pompe disease (PD) is feasible, enabling timely treatment intervention as well as disease incidence estimates, according to an Italian study published in Molecular Genetics and Metabolism Reports.

NBS detected 11 newborns with PD out of 206,741 children born between September 2015 and April 2022 in North East Italy. Of these children, 3 were confirmed to have infantile-onset PD (IOPD), and the other 8 had late-onset PD (LOPD). From this data, regional incidences were estimated to be 1/18,795 for PD overall, 1/68,914 for IOPD, and 1/25,843 for LOPD.

“Our study, the largest reported to date in Europe, demonstrates that PD NBS is feasible and readily extendable to the larger Italian newborn populations,” the authors said.

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Of the patients with IOPD, 2 were male, cross-reactive immunological material (CRIM)-negative, and had hypertrophic cardiomyopathy. The third patient, female and CRIM-positive, was asymptomatic. All had increased levels of muscle necrosis biomarkers, a short PR interval on electrocardiography (ECG), increased left ventricular max index, and molecular analysis, all suggestive of IOPD.

One of the male patients also had heart failure with an ejection fraction of 20%. All 3 patients initiated enzyme replacement therapy (ERT) between 5 and 19 days of life and were still alive at the last follow-up.

Two of the patients had age-appropriate motor development with normal biochemical testing and no signs of cardiomyopathy. The third patient, who presented with heart failure, had stable biomarkers and cardiac parameters but delayed psychomotor development.

“The primary goal of NBS is identifying patients who can benefit from early treatment. Early detection and ERT are certainly beneficial for IOPD patients, but also for less severe LOPD patients,” the researchers continued.

Of the 8 patients with LOPD, 2 had shortened PR intervals on ECG while the rest had normal cardiologic assessments. These 2 patients did not have hypertrophy and their PR intervals normalized on subsequent visits. During the follow-up of up to 5.5 years, none of the patients had developed symptoms nor initiated ERT.

An additional 6 newborns were found to have variants of unknown significance (VUS). All of these infants were asymptomatic and had normal biochemical and cardiac tests at birth and last follow-up.

“Remaining challenges include reducing the number of false positives and determining the best management of infants with suspected LOPD and VUS,” the authors said.


Gragnaniello V, Pijnappel PWWM, Burlina AP, et al. Newborn screening for Pompe disease in Italy: long-term results and future challenges. Mol Genet Metab Rep. Published online October 22, 2022. doi:10.1016/j.ymgmr.2022.100929