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Hyper-IgM Syndrome


James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Last full review/revision Apr 2021| Content last modified Apr 2021

Hyper-IgM syndrome is characterized by normal or high levels of immunoglobulin M (IgM) and decreased levels or absence of other immunoglobulins. As a result, people are more susceptible to bacterial infections.

  • Children with hyper-IgM syndrome have frequent sinus and lung infections.
  • Doctors diagnose the disorder by measuring levels of immunoglobulins in the blood and by doing genetic tests.
  • Treatment involves immune globulin, antibiotics to prevent infections, and, when possible, stem cell transplantation.

(See also Overview of Immunodeficiency Disorders.)

Hyper-IgM syndrome is a primary immunodeficiency disorder. It may be inherited in one of the following ways:

  • As an X-linked disorder: That is, it is due to a mutation in a gene on the X (sex) chromosome. X-linked disorders usually affect only boys.
  • As an autosomal recessive disorder: That is, two genes for the disorder, one from each parent, are required.

Most cases of hyper-IgM syndrome are X-linked.

How the disorder affects people varies depending on which gene is affected.

Levels of IgM may be high or normal. Other immunoglobulins may be absent, or levels may be low. The lack of other immunoglobulins makes people with hyper-IgM syndrome less able to fight off infections.

X-linked hyper-IgM syndrome

In X-linked hyper-IgM syndrome, B cells produce only IgM, not other types of immunoglobulin. Levels of IgM may be normal or high.

Infants with this form often develop pneumonia due to the fungus Pneumocystis jirovecii. Children have frequent sinus and lung infections during the first 2 years of life.

Many children die before puberty, and those who live longer often develop cirrhosis or lymphoma.

Autosomal recessive hyper-IgM syndrome

Generally, symptoms are similar to those of the X-linked form.

There are several autosomal recessive forms. In some of them, the lymph nodes, spleen, and tonsils are enlarged, and autoimmune disorders may develop.

Diagnosis of Hyper-IgM Syndrome

  • Blood tests
  • Genetic testing

Doctors suspect hyper-IgM syndrome based on symptoms. They then measure levels of immunoglobulins. High or normal levels of IgM and low levels or absence of other immunoglobulins support the diagnosis.

When possible, the diagnosis is confirmed by genetic testing.

Prenatal genetic testing can be offered to women considering pregnancy if they have family members with certain gene mutations that can cause hyper-IgM syndrome.

Treatment of Hyper-IgM Syndrome

  • Immune globulin
  • Sometimes an antibiotic to prevent infections
  • Stem cell transplantation when possible

People with hyper-IgM syndrome are usually given immune globulin to replace some of the missing immunoglobulins. Immune globulin consists of antibodies obtained from the blood of people with a normal immune system.

Some people with some forms of this syndrome are given trimethoprim/sulfamethoxazole (an antibiotic) to prevent Pneumocystis jirovecii infection.

Stem cell transplantation from a sibling with the same tissue type is done when possible.

More Information about Hyper-IgM Syndrome

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  • Immune Deficiency Foundation: Hyper-IgM syndrome: Comprehensive information on hyper-IgM syndrome, including information on diagnosis and treatment and advice for people affected

Drugs Mentioned In This Article

Generic Name Select Brand Names
immune globulin Gammagard S/D
trimethoprim No US brand name

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