Hyper IgM syndrome

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Hyper IgM syndrome
Immunoglobulin M
ICD-10 D80.5
ICD-9 279.05
eMedicine ped/2457 
MeSH D053306

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Hyper IgM syndrome is a family of genetic disorders in which the level of Immunoglobulin M (IgM) antibodies is relatively high. The disorder causes immunodeficiencies, including a higher than normal susceptibility to various types of infections. Individuals with hyper-IgM syndrome typically also have a low number of infection-fighting neutrophil cells.


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. Some hyper-IgM syndromes are actually deficiencies of the other immunoglobulin classes: IgA, IgG, and IgE.


Five types have been characterized:

  • Hyper-IgM syndrome type 2, characterized by mutations of the AICDA gene. In this type, B cells cannot recombine genetic material to change heavy chain production, which is a required step in switching classes.
  • Hyper-IgM syndrome type 3, characterized by mutations of the CD40 gene. In this type, B cells cannot receive the signal from T cells to switch classes.

Differentiating Hyper IgM Syndrome From Other Diseases

Hyper IgM syndrome should be differentiated from other disorders leading to defects of humoral immunity. The following conditions may be considered as differentials:[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][25][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]

Disorder Defect (Mechanism of Development) Characteristic Features Clinical Presentation Laboratory Findings
X-Linked (Bruton) Agammaglobulinemia
Selective IgA Deficiency
  • Serum IgA < 7 mg/dl
  • Normal IgG and IgM levels
Common Variable Immunodeficiency
  • Defective B cell differentiation
  • May be acquired in 20-30 years of age
Autosomal dominant hype IgE syndrome (Job's Syndrome)
  • Distinctive coarse facies
  • Cold (non-inflammatory) Staphylococcal abscesses
  • Retained primary teeth
  • Eczema
Severe combined immunodeficiency (SCID)
Ataxia Telangiectasia
Hyper IgM Syndrome
Wiskott-Aldrich Syndrome
  • Malignancy: can cause the reduction in the immunoglobulin production.[52]
  • Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia..
  • Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.[53]
  • Other causes of primary humoral immunodeficiencies.
  • Smoking: may cause IgG2 subclass deficiency.[54]


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