Autosomal recessive hyper-IgE syndrome

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What is autosomal recessive hyper-IgE syndrome?

Autosomal recessive hyper-IgE syndrome (AR-HIES) is a disorder of the immune system. A hallmark feature of the condition is recurrent infections that are severe and can be life-threatening. Skin infections can be caused by bacteria, viruses, or fungi. These infections cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling. People with AR-HIES also tend to have frequent bouts of pneumonia and other respiratory tract infections.

Other immune system-related problems in people with AR-HIES include an inflammatory skin disorder called eczema, food or environmental allergies, and asthma. In some affected individuals, the immune system malfunctions and attacks the body's own tissues and organs, causing autoimmune disease. For example, autoimmunity can lead to abnormal destruction of red blood cells (hemolytic anemia) in people with AR-HIES.

AR-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood; the levels are more than 10 times higher than normal. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with AR-HIES have such high levels of this protein. People with AR-HIES also have highly elevated numbers of certain white blood cells called eosinophils (hypereosinophilia). Eosinophils aid in the immune response and are involved in allergic reactions.

Some people with AR-HIES have neurological problems, such as paralysis that affects the face or one side of the body (hemiplegia). Blockage of blood flow in the brain or abnormal bleeding in the brain, both of which can lead to stroke, can also occur in AR-HIES.

People with AR-HIES have a greater-than-average risk of developing cancer, particularly cancers of the blood or skin.

How common is autosomal recessive hyper-IgE syndrome?

AR-HIES is a rare disorder whose prevalence is unknown.

What genes are related to autosomal recessive hyper-IgE syndrome?

AR-HIES is usually caused by mutations in the DOCK8 gene. The protein produced from this gene plays a critical role in the survival and function of several types of immune system cells. One of the protein's functions is to help maintain the structure and integrity of immune cells called T cells and NK cells, which recognize and attack foreign invaders, particularly as these cells travel to sites of infection within the body. In addition, DOCK8 is involved in chemical signaling pathways that stimulate other immune cells called B cells to mature and produce antibodies, which are specialized proteins that attach to foreign particles and germs, marking them for destruction.

DOCK8 gene mutations result in the production of little or no functional DOCK8 protein. Shortage of this protein impairs normal immune cell development and function. It is thought that T cells and NK cells lacking DOCK8 cannot maintain their shape as they move through dense spaces, such as those found within the skin. The abnormal cells die, resulting in reduced numbers of these cells. A shortage of these immune cells impairs the immune response to foreign invaders, accounting for the severe viral skin infections common in AR-HIES. A lack of DOCK8 also impairs B cell maturation and the production of antibodies. A lack of this type of immune response leads to recurrent respiratory tract infections in people with this disorder. It is unclear how DOCK8 gene mutations are involved in other features of AR-HIES, such as the elevation of IgE levels, autoimmunity, and neurological problems.

Some people with AR-HIES do not have mutations in the DOCK8 gene. The genetic cause of the condition in these individuals is unknown.

How do people inherit autosomal recessive hyper-IgE syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of autosomal recessive hyper-IgE syndrome?

These resources address the diagnosis or management of autosomal recessive hyper-IgE syndrome and may include treatment providers.

You might also find information on the diagnosis or management of autosomal recessive hyper-IgE syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about autosomal recessive hyper-IgE syndrome?

You may find the following resources about autosomal recessive hyper-IgE syndrome helpful. These materials are written for the general public.

MedlinePlus - Health information (5 links)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases
Additional NIH Resources - National Institutes of Health (2 links)
Educational resources - Information pages (4 links)
Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for autosomal recessive hyper-IgE syndrome?

AR-HIES
autosomal recessive HIES
CID due to DOCK8 deficiency
combined immunodeficiency due to DOCK8 deficiency
DOCK8 deficiency
DOCK8 immunodeficiency syndrome
hyper IgE recurrent infection syndrome, autosomal recessive
hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive
hyper immunoglobulin E syndrome, autosomal recessive
hyperimmunoglobulin E syndrome type 2
non-skeletal hyper-IgE syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about autosomal recessive hyper-IgE syndrome?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding autosomal recessive hyper-IgE syndrome?

anemia ; autoimmune ; autoimmune disease ; autoimmunity ; autosomal ; autosomal recessive ;bacteria ; cancer ; cell ; deficiency ; eczema ; eosinophils ; gene ; hemiplegia ; hemolytic anemia ;immune response ; immune system ; immunodeficiency ; immunoglobulin ; infection ; inherited ;neurological ; NK cells ; pneumonia ; prevalence ; protein ; recessive ; respiratory ; syndrome ;white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (6 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook