Hyper IgM syndrome

December 31, 2014

Overview

A rare inherited immunodeficiency disorder which causes frequent infections involving the ears, eyes, sinuses, lungs, skin, respiratory tract and other areas of the body. This condition is inherited in an X-linked recessive pattern.

X-linked hyper IgM syndrome is a condition that affects the immune system and occurs almost exclusively in males. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. There are several classes of antibodies, and each one has a different function in the immune system. Although the name of this condition implies that affected individuals always have high levels of immunoglobulin M (IgM), some people have normal levels of this antibody. People with X-linked hyper IgM syndrome have low levels of three other classes of antibodies: immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). The lack of certain antibody classes makes it difficult for people with this disorder to fight off infections.

Symptoms

Recurring respiratory infections
Enlarged tonsils
Enlarged liver
Enlarged spleen
Chronic diarrhea

Causes

Mutations in the CD40LG gene cause X-linked hyper IgM syndrome. This gene provides instructions for making a protein called CD40 ligand, which is found on the surface of immune system cells known as T cells. CD40 ligand attaches like a key in a lock to its receptor protein, which is located on the surface of immune system cells called B cells. B cells are involved in the production of antibodies, and initially they are able to make only IgM antibodies. When CD40 ligand and its receptor protein are connected, they trigger a series of chemical signals that instruct the B cell to start making IgG, IgA, or IgE antibodies.

CD40 ligand is also necessary for T cells to interact with other cells of the immune system, and it plays a key role in T cell differentiation (the process by which cells mature to carry out specific functions).

Mutations in the CD40LG gene lead to the production of an abnormal CD40 ligand or prevent production of this protein. If CD40 ligand does not attach to its receptor on B cells, these cells cannot produce IgG, IgA, or IgE antibodies. Mutations in the CD40LG gene also impair the T cell's ability to differentiate and interact with other immune system cells. People with X-linked hyper IgM syndrome are more susceptible to infections because they do not have a properly functioning immune system.

Diagnosis

The signs and symptom information on this page attempts to provide a list of some possible signs and symptoms of Hyper-IgM Syndrome. This medical information about signs and symptoms for Hyper-IgM Syndrome has been gathered from various sources, may not be fully accurate, and may not be the full list of Hyper-IgM Syndrome signs or Hyper-IgM Syndrome symptoms. Furthermore, signs and symptoms of Hyper-IgM Syndrome may vary on an individual basis for each patient. Only your doctor can provide adequate diagnosis of any signs or symptoms and whether they are indeed Hyper-IgM Syndrome symptoms