Pompe disease, also known as glycogen storage disease type II (GSD II), is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid-α-glucosidase. This enzyme deficiency leads to generalized accumulation of lysosomal glycogen in the body. Diagnostic testing of Pompe disease generally consists of the determination of acid-α-glucosidase enzyme activity followed by genetic confirmation testing.

Pompe disease is commonly classified based on the age of onset as infantile (IOPD/classic Pompe disease) when presenting during the first year of life, and late-onset (LOPD) when it presents afterward. Classic Pompe disease typically presents in the first weeks of life with hypotonia, and progressive muscle weakness (common symptoms of other muscular disorders), as well as macroglossia and hepatomegaly.

In a collaborative study between ARCHIMEDlife and the Newborn Screening Unit of the Hamburg University Medical Center, a cohort of 13,627 samples were tested between January 2017 and December 2018 for acid-α-glucosidase deficiency using either fluorometry or tandem mass spectrometry (MS). Targeted screening (at-risk testing) was performed for patients who displayed conditions of unknown etiology, such as CK elevations or cardiomyopathy, in the case of infantile patients.

Targeted screening (or at-risk testing) yields immediate benefits for patients regarding the availability and timeliness of a diagnosis.

On average 8% of samples showed activity below the reference range and were further assessed by another enzyme activity measurement or molecular genetic analysis. Pre-analytical conditions, like proper drying, greatly affect enzyme activity and should be assessed with measurement of reference enzyme(s).

Our results show that targeted screening can provide a good first step for the future introduction of newborn screening for Pompe disease. Additionally, it provides immediate benefits for the patients regarding the availability and timeliness of the diagnosis.

Read the whole publication in the International Journal of Newborn Screening.


The publication of this paper is a special honor to our friend and colleague, Dr. Zoltan Lukacs, who dedicated his whole life to newborn screening, rare diseases, and diagnostics of rare diseases. We still cannot realize the tragic loss of such a great person.

All of us at ARCHIMEDlife would like to extend a special thank you to the International Journal of Newborn Screening for helping to make this publication happen.