Strong Genetic

Pompe Disease (Glycogen Storage Disease Type II)

Name: Pompe Disease (Glycogen Storage Disease Type II)
Creator: Realised
Published: 2026-03-01

GeneGAArsIDrs28940868, rs121907928, rs28940871, rs121907927, rs386834236InheritanceAutosomal recessiveCarrier frequency~1 in 100-150 general population (higher in African Americans ~1 in 40 for certain variants, Dutch ~1 in 50 for late-onset variant)SystemCarrier Screening

Summary

Pompe disease is a lysosomal storage disorder where deficiency of the enzyme acid alpha-glucosidase causes glycogen to accumulate in cells — particularly muscle cells, including the heart and skeletal muscles. The condition exists on a spectrum from severe infantile-onset to milder late-onset forms.

Practical takeaway

This matters when planning children. Pompe disease carrier frequency varies by population but is not uncommon — particularly in African American and Northern European (especially Dutch) populations. A carrier test through a GP or genetic counselling service can determine your partner's status. If you are both carriers, a genetic counsellor can discuss the expected severity based on your specific variant combination, the availability of newborn screening, and the treatment landscape including enzyme replacement therapy. The reassuring context is that Pompe disease is treatable, newborn screening enables early intervention, and outcomes have improved dramatically. Realised does not calculate reproductive risk or advise on reproductive decisions.

Evidence detail

What Carrier Status Means For You

You are not affected. One working copy of GAA produces sufficient acid alpha-glucosidase for normal glycogen processing. Your carrier status becomes relevant if your partner also carries a GAA variant. In that case, each child has a 25% chance of having Pompe disease, a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither variant. The clinical severity would depend on which specific combination of variants a child inherits.

Population Context

Pompe disease carrier frequency varies significantly across populations. The c.-32-13T>G variant (the most common late-onset variant) is particularly prevalent in Dutch and broader Northern European populations, with a carrier frequency of approximately 1 in 50 in the Netherlands. Certain severe variants are more common in African American populations, with carrier frequencies as high as 1 in 40. The condition occurs in all ethnic groups. Combined, Pompe disease is one of the more common lysosomal storage disorders, with an estimated total incidence of 1 in 40,000 births. Newborn screening has enabled presymptomatic treatment and significantly improved outcomes.

Limitations

23andMe tests 5 of over 600 known pathogenic GAA variants. The tested panel covers some of the most common variants in European and African American populations, but the extreme genetic heterogeneity of Pompe disease means most pathogenic variants are not captured by consumer testing. A "not detected" result provides only modest reduction in carrier risk. Comprehensive carrier screening through a clinical laboratory, or enzymatic testing (measuring GAA enzyme activity), provides substantially higher sensitivity. This is particularly important because Pompe disease is treatable — early identification via carrier testing or newborn screening directly impacts outcomes.

Sources (7)

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