Hyper IgM syndrome is a family of genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

s in which the level of Immunoglobulin M

Immunoglobulin M

Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...

 (IgM) antibodies

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 is relatively high. The most common type is a result of a defect in a Th2 cell protein (CD40 ligand). The disorder causes immunodeficiencies

Immunodeficiency

Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...

, including a higher than normal susceptibility to various types of infections. Individuals with hyper-IgM syndrome typically also have a low number of neutrophils and platelet

Platelet

Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days...

s.

Pathophysiology

IgM is the form of antibody that all B cells produce initially, before they undergo class switching due to exposure to a recognized antigen. Healthy B cells efficiently switch to other types of antibodies as needed to attack invading bacteria, viruses, and other pathogens. Generally, in people with hyper IgM syndromes, the B cells keep making IgM antibodies because they can't switch to a different kind of antibody. This results in an overproduction of IgM antibodies and an underproduction of all other types, IgA, IgG, and IgE.

Types

Five types have been characterized:

• Hyper-IgM syndrome type 1, characterized by mutations of the CD40LG gene. In this type, T cells cannot tell B cells to switch classes.

• Hyper-IgM syndrome type 2, characterized by mutations of the AICDA
  AICDA
  Activation-induced cytidine deaminase, also known as AICDA and AID, is an enzyme which in humans is encoded by the AICDA gene.- Function :This gene encodes a RNA-editing deaminase that is a member of the cytidine deaminase family...
  
  gene. In this type, B cells cannot recombine genetic material to change heavy chain
  Heavy chain
  ]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...
  
   production, which is a required step in switching classes.

• Hyper-IgM syndrome type 3
  Hyper-IgM syndrome type 3
  Hyper-IgM syndrome type 3 is a form of Hyper IgM syndrome characterized by mutations of the CD40 gene. In this type, B cells cannot receive the signal from T cells to switch classes....
  
  , characterized by mutations of the CD40 gene. In this type, B cells cannot receive the signal from T cells to switch classes.

• Hyper-IgM syndrome type 4
  Hyper-IgM syndrome type 4
  Hyper-IgM syndrome type 4 is a form of Hyper IgM syndrome which is a defect in class switch recombination downstream of the AICDA gene that does not impair somatic hypermutation....
  
  , which is a defect in class switch recombination downstream of the AICDA
  AICDA
  Activation-induced cytidine deaminase, also known as AICDA and AID, is an enzyme which in humans is encoded by the AICDA gene.- Function :This gene encodes a RNA-editing deaminase that is a member of the cytidine deaminase family...
  
   gene that does not impair Somatic Hyper Mutation.

• Hyper-IgM syndrome type 5, characterized by mutations of the UNG gene.

Pneumocystis pneumonia

Infections with Pneumocystis pneumonia

Pneumocystis pneumonia

Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...

are common in infants with Hyper IgM syndrome.

External links

• GeneReviews/NCBI/NIH/UW entry on X-Linked Hyper IgM Syndrome or Immunodeficiency with Hyper-IgM, Type 1