Name: Hyper-IgM syndrome type 2 | Acronym: HIGM2a
Alt. names: Immunodeficiency with hyper-IgM, type 2a

Gene: AICDA | MOI: Autosomal recessive | Mechanism of action:

No. of cases in DB: 2 | First reported in: 2000

Last updated on: 2024-03-07 09:20:54 by Andrés Caballero-Oteyza

OMIM: 605258

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Immunodeficiency caused by biallelic mutations in the AICDA gene. It is characterized by normal or elevated concentrations of IgM and decreased or absent concentrations of IgG, IgA, and IgE. Elevated IgM levels are due to absence of immunoglobulin class-switch recombination and the lack of immunoglobulin somatic hypermutations. Patients show lymph node hyperplasia caused by the presence of giant germinal centers. Individuals are highly susceptible to severe bacterial infections (i.e. bacterial, sino-respiratory and gastrointestinal tract infections). None of the patients had a history of opportunistic infection, in contrast to patients with HIGM1 (due to X-linked CD40LG mutations) or HIGM3 (due to AR CD40 mutations). Minegishi et al. (2000) noted that, compared to other hyper-IgM genotypes, their cohort of 18 patients tended to be older at the age of diagnosis, were more likely to have positive isohemagglutinins, and were less likely to have anemia, neutropenia, or thrombocytopenia. However, further expansion of the phenotype by Quartier et al. (2004) did find that patients developed recurrent and severe infections, as well as autoimmune or inflammatory disorders including diabetes mellitus, polyarthritis, autoimmune hepatitis, hemolytic anemia, immune thrombocytopenia, Crohn's disease and chronic uveitis (PMID: 14962793). Ouadani et al. (2016) studied a cohort of Tunisian AID-deficient patients and noted that they do not classically develop intracellular infections such as Mycobacteria (PMID: 26545377) and that AICDA mutations were the predominant genotype found in Tunisians with HIGM.

Antiinfectious prophylaxis (including with IVIG, which has been reported to be effective) and early and aggressive treatment of infections may be beneficial; Individuals may also have autoimmune and inflammatory manifestations, some of which may benefit from early knowledge and interventions, including hemolytic anemia and immune thrombocytopenia.