A rare hyperthyroidism characterized by mild to severe hyperthyroidism, presence of goiter, absence of features of autoimmunity, frequent relapses while on treatment and a positive family history.

A rare, autosomal recessive inherited disorder usually caused by mutations in the THRB gene. It is characterized by a defective physiological resistance to thyroid hormones, resulting in the elevation of thyroxin and triiodothyronine in the serum.

Common variable immunodeficiency-10 (CVID10) is an autosomal dominant primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency (summary by Chen et al., 2013). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).

Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is an autosomal dominant disorder with onset in early infancy. Affected individuals develop severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency (summary by Poli et al., 2018). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).

Immunodeficiency-64 with lymphoproliferation (IMD64) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show variably decreased numbers of T cells, with lesser deficiencies of B and NK cells. There is impaired T-cell proliferation and activation; functional defects in B cells and NK cells may also be observed. Patients have increased susceptibility to EBV infection and may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity (summary by Salzer et al., 2016, Mao et al., 2018, and Winter et al., 2018).

Immunodeficiency-89 and autoimmunity (IMD89) is an autosomal recessive immune disorder characterized by adult onset of recurrent infections, allergies, microcytic anemia, and Crohn disease (see 266600) (Yang et al., 2020).

X-linked multisystem autoinflammatory disease with immune dysregulation (ADMIDX) is an X-linked recessive disorder with onset of symptoms in infancy or early childhood. Affected individuals may present with variable cytopenias, including anemia, thrombocytopenia, neutropenia, lymphopenia, or hypogammaglobulinemia, and systemic or organ-specific autoinflammatory manifestations. These include skin lesions, panniculitis, inflammatory bowel disease, pulmonary disease, or arthritis associated with recurrent fever, leukocytosis, lymphoproliferation, and hepatosplenomegaly in the absence of an infectious agent. Some patients have circulating autoantibodies that underlie the cytopenias or systemic features, whereas others do not have circulating autoantibodies. In addition, some patients have recurrent infections, whereas others do not show signs of an immunodeficiency. Laboratory studies are consistent with immune dysregulation, including altered B-cell subsets and variably elevated proinflammatory cytokines. Detailed functional studies of platelets, red cells, and T lymphocytes suggest that abnormal actin cytoskeleton remodeling is a basic defect, indicating that this disorder can be classified as an immune-related actinopathy. Severe complications of the disease may result in death in childhood (Boussard et al., 2023; Block et al., 2023).