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Disease Profile

Immunodeficiency with hyper IgM type 1

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

X-linked hyper IgM syndrome; Hyper IgM immunodeficiency, x-linked; Hyper IgM syndrome;


Congenital and Genetic Diseases; Immune System Diseases


Hyper IgM syndrome is a type of primary immunodeficiency syndrome. Primary immunodeficiency occurs when part of a person’s immune system is missing or does not work correctly. The bodies of people with primary immunodeficiency can’t get rid of germs or protect themselves from new germs as well as they should. Primary immunodeficiencies are inherited, meaning they are passed down from parents to children.[1]

Hyper IgM syndromes are characterized by normal or elevated serum immunoglobulin M levels with absence of immunoglobulin G, A, and E. Immunoglobulins are proteins found in the blood. Hyper IgM results in a susceptibility to bacterial infections and sometimes opportunistic infections. There are five different types of hyper IgM syndromes (types 1-5). The types are distinguished by the location of the gene mutation involved.[2]


Symptoms and physical findings associated with hyper IgM syndrome usually become apparent in the first or second year of life.[3][4] This condition may be characterized by recurrent pus-producing (pyogenic) bacterial infections of the upper and lower respiratory tract including the sinuses (sinusitis) and/or the lungs (pneumonitis or pneumonia); the middle ear (otitis media); the membrane that lines the eyelids and the white portions (sclera) of the eyes (conjunctivitis); the skin (pyoderma); and/or, in some cases, other areas.[5][3][4]

Other signs of the disease include enlarged tonsils, liver, and spleen, chronic diarrhea, and an increased risk of unusual or “opportunistic” infections and non-Hodgkins lymphoma.[5][3][4] Opportunistic infections are infections caused by microorganisms that usually do not cause disease in individuals with fully functioning immune systems (non-immunocompromised) or widespread (systemic) overwhelming disease by microorganisms that typically cause only localized, mild infections. In individuals with Hyper-IgM Syndrome, such opportunistic infections may include those caused by Pneumocystis carinii, a microorganism that causes a form of pneumonia, or Cryptosporidium, a single-celled parasite (protozoa) that can cause infections of the intestinal tract.[4]

In addition, individuals with Hyper-IgM Syndrome are prone to certain autoimmune disorders affecting particular elements of the blood. Autoimmune attacks on red blood cells lead to anemia, while autoimmune destruction of infection-fighting neutrophils further increases the risk of infection.[5][4]

The range and severity of symptoms and physical features associated with this disorder may vary from case to case.[4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
1%-4% of people have these symptoms
Scar tissue replaces healthy tissue in the liver
Watery stool
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Liver inflammation
Low blood neutrophil count
Low neutrophil count

[ more ]

Oral ulcer
Mouth ulcer
Recurrent lower respiratory tract infections
Recurrent chest infections
Sclerosing cholangitis
Infection in blood stream
Percent of people who have these symptoms is not available through HPO
Absence of lymph node germinal center
Autoimmune hemolytic anemia
Autoimmune thrombocytopenia
Autosomal recessive inheritance
Permanent enlargement of the airways of the lungs
Chronic hepatitis
Chronic liver inflammation
Decreased circulating IgA level
Decreased circulating IgE
Decreased circulating IgG level
Decreased T cell activation
Enlarged tonsils
Inflamed gums
Red and swollen gums

[ more ]

Hemolytic anemia
Enlarged liver
Decreased immune function
Impaired Ig class switch recombination
Impaired memory B cell generation
Increased circulating IgM level
Swollen lymph nodes
Bone infection
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

Recurrent infection of the gastrointestinal tract
Recurrent gastrointestinal infections
Recurrent upper and lower respiratory tract infections
Recurrent upper respiratory tract infections
Recurrent colds
Increased spleen size
Inflammation of the mouth
Low platelet count
X-linked recessive inheritance


A flawed gene (or genes) in Tcells (a type of white blood cell that is part of the immune system and helps the body fight diseases or harmful substances) is responsible for hyper IgM syndrome. The faulty T-cells do not give B-cells a signal they need to switch from making IgM to IgA and IgG. Most cases (approximately 70%) of hyper-IgM syndrome are linked to a recessive mutation on the X chromosome. These cases are inherited as an X-linked recessive genetic trait. Because males do not have a second, healthy, Xchromosome to offset the disease, boys far out number girls with this disease.[5][3][4]

A small number of cases of hyper IgM syndrome have been attributed to autosomal recessive and autosomal dominant genetic inheritance. In addition, a rare acquired form of the disorder has been described in the medical literature.[4]


Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    The cornerstone of treatment for individuals with hyper IgM syndrome is regular injections of intravenous immunogloblulin (IVIG). This treatment not only supplies missing IgG antibodies, but also prompts a drop in IgM antibodies.[5][3] Patients with neutropenia can take granulocyte colony-stimulating factor (G-CSF). Antibiotics may also be prescribed to prevent the respiratory infection, pneumocystis carinii pneumonia.[3]

    Most children with hyper-IgM syndrome respond well to treatment, become symptom-free and resume normal growth.[5]


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Immunodeficiency with hyper IgM type 1. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Merck Manual for health care professionals provides information on Immunodeficiency with hyper IgM type 1.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            The Online Mendelian Inheritance in Man (OMIM)
            The Online Mendelian Inheritance in Man (OMIM)
            The Online Mendelian Inheritance in Man (OMIM)
            The Online Mendelian Inheritance in Man (OMIM)
            The Online Mendelian Inheritance in Man (OMIM)
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Immunodeficiency with hyper IgM type 1. Click on the link to view a sample search on this topic.


            1. Primary Immunodeficiency. National Institute of Child Health and Human Development (NICHD). April 7, 2008; https://www.nichd.nih.gov/publications/pubs/pages/primary_immuno.aspx#WhatisPrimaryImmunodeficiency.
            2. Hyper IgM Immunodeficiency Syndrome. MeSH. https://www.nlm.nih.gov/cgi/mesh/2008/MB_cgi?mode=&index=24001&field=all&HM=&II=&PA=&form=&input=. Accessed 4/16/2008.
            3. Hyper IgM Immunodeficiency. Primary Immunodeficiency Resource Center. 2008; https://www.info4pi.org/aboutPI/index.cfm?section=aboutPI&content=syndromes&area=13&CFID=4740438&CFTOKEN=e428d93702237370-4B49B0F6-0023-0F1A-C289B29F1FE43C9A. Accessed 4/16/2008.
            4. Hyper IgM Syndrome. National Organization for Rare Disorders (NORD). 2002; https://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Hyper%20IgM%20Syndrome. Accessed 4/16/2008.
            5. Primary Immunodeficiency Diseases: Some Examples. National Institute of Child Health and Human Development (NICHD). April 7, 2008; https://www.nichd.nih.gov/publications/pubs/pages/primary_immuno.aspx. Accessed 4/16/2008.

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