MedGen

XMEN is an X-linked recessive immunodeficiency characterized by CD4 (186940) lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation (Li et al., 2011). Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders. Magnesium supplementation may be therapeutic (summary by Li et al., 2014). [from OMIM]

IMD23 is an autosomal recessive primary immunodeficiency syndrome characterized by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity (summary by Bjorksten and Lundmark, 1976 and Zhang et al., 2014). [from OMIM]

Immunodeficiency-41 is an autosomal recessive complex disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation (summary by Goudy et al., 2013). [from OMIM]

Lymphoproliferative syndrome-2, also known as CD27 deficiency, is an autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impairment in specific antibody function resulting from impaired T cell-dependent B-cell responses and T-cell dysfunction (summary by van Montfrans et al., 2012). The phenotype can vary significantly, from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation (summary by Salzer et al., 2013). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240). [from OMIM]

Immunodeficiency-73B with defective neutrophil chemotaxis (IMD73B) is an autosomal dominant immunologic disorder characterized by onset of recurrent infections in infancy or early childhood. Affected individuals develop respiratory infections, cellulitis, and severe invasive infections or sepsis; organisms include bacteria such as Staphylococcus, as well as viruses, fungi, and mycobacterial species. Laboratory studies show variable abnormalities, including B- and T-cell lymphopenia, decreased immunoglobulin subsets, decreased TRECs and dysfunctional T cells, decreased NK cells, neutropenia, and impaired neutrophil chemotaxis. Hematopoietic stem cell transplantation is curative (summary by Hsu et al., 2019; review by Lougaris et al., 2020). In a review of autosomal forms of chronic granulomatous disease (see 306400 for genetic heterogeneity of CGD), Roos et al. (2021) noted that patients with RAC2 mutations may manifest CGD-like symptoms due to defects in neutrophil NADPH oxidase activity. [from OMIM]

A rare genetic disease characterized by infantile onset of severe inflammatory bowel disease manifesting with bloody diarrhea and failure to thrive, and central nervous system disease with global developmental delay and regression, impaired speech, hypotonia, hyperreflexia, and epilepsy. Brain imaging shows global cerebral atrophy, thin corpus callosum, delayed myelination, and posterior leukoencephalopathy. Cases with recurrent infections and impaired T-cell responses to stimulation, as well as decreased T-cell subsets, have been reported. [from ORDO]

IMD24 is an autosomal recessive immunodeficiency characterized by the impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpesviruses, including Epstein-Barr virus (EBV) and varicella zoster virus (VZV); they also suffer from recurrent encapsulated bacterial infections, a spectrum typical of a combined deficiency of adaptive immunity (CID) (summary by Martin et al., 2014). [from OMIM]

Immunodeficiency-40 is an autosomal recessive primary form of combined immunodeficiency mainly affecting T-cell number and function, with other more variable defects in B-cell and NK-cell function. Patients have onset of severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation (summary by Dobbs et al., 2015). [from OMIM]

Immunodeficiency-20 is a rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Patient NK cells are defective in spontaneous cell cytotoxicity, but retain antibody-dependent cellular cytotoxicity. Patients typically present early in childhood with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV) (summary by Grier et al., 2012). [from OMIM]

Lymphoproliferative syndrome-3 (LPFS3) is an autosomal recessive early-onset immunologic disorder characterized by increased susceptibility to Epstein-Barr virus (EBV) infection in B cells, resulting in abnormal B-cell proliferation and increased susceptibility to B-cell malignancies, including Hodgkin lymphoma. Patients usually have hypogammaglobulinemia without lymphopenia, although some subsets of immune cells may be low and some patients may have recurrent infections. The disorder results from impaired signaling from proliferating B cells to effector T cells that provide immune surveillance. There may be an increased risk of solid tumors in heterozygous carriers (summary by Abolhassani et al., 2017). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240). [from OMIM]

Immunodeficiency-7 (IMD7) is an autosomal recessive immunologic disorder characterized by onset of recurrent bacterial and viral infections in infancy or early childhood. Affected individuals may also have features of immune dysregulation, including lymphadenopathy and presence of autoantibodies. Laboratory studies show increased serum IgE, low numbers of T cells, low TCR-alpha/beta cells, and increased TCR-gamma/delta cells. The disorder often results in death in childhood, although bone marrow transplant is effective (summary by Morgan et al., 2011 and Rawat et al., 2021). [from OMIM]

Immunodeficiency-102 (IMD102) is an X-linked recessive immunologic disorder characterized by the onset of recurrent sinopulmonary, mucosal, and other infections in early childhood, usually accompanied by refractory autoimmune cytopenias. Affected individuals have bacterial, viral, and fungal infections, as well as hemolytic anemia, thrombocytopenia, lymphopenia, and decreased NK cells. Laboratory studies show defective T-cell proliferation and function, likely due to signaling abnormalities. The disorder may also manifest as a hyperinflammatory state with immune dysregulation (Delmonte et al., 2021). [from OMIM]