Strong Genetic

PMM2-Congenital Disorder of Glycosylation (PMM2-CDG, formerly CDG-Ia)

Name: PMM2-Congenital Disorder of Glycosylation (PMM2-CDG, formerly CDG-Ia)
Creator: Realised
Published: 2026-03-01

GenePMM2rsIDrs28936415, rs80338701InheritanceAutosomal recessiveCarrier frequency~1 in 60-80 Europeans (R141H alone ~1 in 60 Danish)SystemCarrier Screening

Summary

PMM2-CDG is the most common congenital disorder of glycosylation, accounting for over 70% of all CDG cases. The PMM2 enzyme is essential for N-glycosylation — the process of attaching sugar chains to proteins throughout the body. When this process fails, hundreds of glycoproteins malfunction simultaneously, producing a multi-system disorder.

Practical takeaway

This matters when planning children. With a European carrier frequency of approximately 1 in 60-80 (based on R141H frequency alone), the chance of a European partner being a carrier is meaningful. 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 severity spectrum, the R141H homozygosity issue, prenatal testing options, and the current management landscape. The diagnosis can be confirmed biochemically (transferrin isoelectric focusing) and genetically. 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 PMM2 produces sufficient phosphomannomutase for normal glycosylation. Your carrier status becomes relevant if your partner also carries a PMM2 variant. In that case, each child has a 25% chance of having PMM2-CDG, a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither variant. If both parents carry R141H specifically, the expected proportions are modified: R141H/R141H is lethal, so among live-born children, the risk of an affected child is lower than the standard 25% for each pregnancy that progresses.

Population Context

PMM2-CDG is the most common congenital disorder of glycosylation worldwide. The R141H variant is found across European populations, with particularly well-studied carrier frequencies in Scandinavian countries — approximately 1 in 60 in Denmark. The F119L variant is the second most common in Europeans. PMM2-CDG has been reported in diverse ethnic groups, though carrier frequency data is most robust for European populations. Over 1,000 affected individuals have been reported worldwide.

Limitations

23andMe tests 2 of over 110 known pathogenic PMM2 variants. R141H alone accounts for approximately 20% of all disease alleles, and F119L is the second most common European variant, so coverage of the most prevalent alleles is reasonable. However, the condition is genetically heterogeneous and many pathogenic variants are not captured. A "not detected" result provides partial but not comprehensive reduction in carrier risk. Comprehensive carrier screening through a clinical laboratory covers substantially more variants and is recommended if a partner is a known carrier or if there is family history of CDG.

Sources (5)

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