immunodeficiency with hyper-IgM

Definition: HIGM is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections and an increased susceptibility to opportunistic infections.

In addition to HIGM1, other forms of HIGM include HIGM2 (MIM.605258), which results from mutation in the AICDA gene (MIM.605257), HIGM3 (MIM.606843), which results from mutation in the CD40 gene (MIM.109535), and HIGM5 (MIM.608106), which results from mutation in the UNG gene (MIM.191525). No gene is known in 2010 for HIGM4 (MIM.608184).

Types

 immunodeficiency with hyper-IgM type 1 / HIGM1 (MIM.308230) at Xq26
 immunodeficiency with hyper-IgM type 2 / HIGM2 (MIM.605258) at 12p13
 immunodeficiency with hyper-IgM type 3 / HIGM3 (MIM.606843) at 20q12-q13.2
 immunodeficiency with hyper-IgM type 4 / HIGM4 (MIM.608184)
 immunodeficiency with hyper-IgM type 5 / HIGM5 (MIM.608106) at 12q23-q24.1

Synopsis

 X-linked recessive
 Tonsillar hypertrophy
 Gingivitis
 Ulcerative stomatitis
 Hepatomegaly
 Chronic hepatitis
 Splenomegaly
 Diarrhea
 Proctitis
 Neutropenia, chronic or cyclic
 Anemia
 Hemolytic anemia
 Thrombocytopenia
 Immunodeficiency
 Dysgammaglobulinemia
 Primary dysfunction of B-lymphocyte isotype switching and memory B-cell generation
 Lymph nodes lack germinal centers
 Normal or increased IgM
 Serum IgA, IgG, and IgE severely deficient
 B-cell count normal
 Decreased T cell activation
 Recurrent bacterial infections with onset in the first or second year of life
 Pneumocytosis carinii infection (12 to 42%)
 Opportunistic infections

Etiology

 HIGM1 is caused by mutations in the tumor necrosis factor ligand superfamily, member 5 gene (TNFSF5, 308230.0001)

See also

 immunodeficiencies

• constitutional immunodeficiencies (genetic immunodeficiencies)