Disease Directory Hyper IgM Syndrome
Immune

Hyper IgM Syndrome

Also known as: HIGM, CD40L deficiency, CD40 ligand deficiency

Prevalence

1 in 500,000-1,000,000

Onset

Infancy to early childhood

Type

Combined primary immunodeficiency (class-switch recombination defect)

Gene

CD40LG, AID, UNG

About Hyper IgM Syndrome

Hyper IgM Syndrome is a group of rare primary immunodeficiencies characterized by elevated or normal serum IgM with markedly reduced or absent IgG, IgA, and IgE, caused by defects in the molecular machinery required for B-cell class-switch recombination. The most common form is X-linked, caused by mutations in CD40LG encoding CD40 ligand, and predisposes patients to opportunistic infections including Pneumocystis jirovecii pneumonia and Cryptosporidium cholangiopathy. Hematopoietic stem cell transplantation is the only curative option currently available for CD40L deficiency.

Common Clinical Features

Recurrent Pneumocystis jirovecii pneumonia Cryptosporidium-associated sclerosing cholangitis Neutropenia (autoimmune or cyclic) Markedly elevated serum IgM with absent IgG/IgA/IgE Recurrent oral ulcers and gingivitis Susceptibility to opportunistic fungal and viral infections Progressive liver disease from biliary complications

Clinical Trial Eligibility Tips

What to know before applying to Hyper IgM Syndrome trials.

Confirm the specific molecular defect (CD40LG, AID, UNG, or other) as gene therapy trials are mutation-specific and not interchangeable across HIGM subtypes

Active Cryptosporidium infection or established biliary cirrhosis may exclude from transplant conditioning trials — current liver function tests and imaging are essential

Neutropenia trials may co-enroll HIGM patients; document ANC nadir and G-CSF use history

Patient Resources

Patient Organization

Immune Deficiency Foundation

Visit website ↗

Natural History Registry

USIDNET Registry

Join registry ↗

Orphanet

European reference resource for rare diseases (ORPHA:183)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Hyper IgM Syndrome trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Hyper IgM Syndrome. Updated daily.

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