MedGen

X-linked agammaglobulinemia (XLA) is characterized by recurrent bacterial infections in affected males in the first two years of life. Recurrent otitis is the most common infection prior to diagnosis. Conjunctivitis, sinopulmonary infections, diarrhea, and skin infections are also frequently seen. Approximately 60% of individuals with XLA are recognized as having immunodeficiency when they develop a severe, life-threatening infection such as pneumonia, empyema, meningitis, sepsis, cellulitis, or septic arthritis. S pneumoniae and H influenzae are the most common organisms found prior to diagnosis and may continue to cause sinusitis and otitis after diagnosis and the initiation of gammaglobulin substitution therapy. Severe, difficult-to-treat enteroviral infections (often manifest as dermatomyositis or chronic meningoencephalitis) can be prevented by this treatment. The prognosis for individuals with XLA has improved markedly in the last 25 years as a result of earlier diagnosis, the development of preparations of gammaglobulin that allow normal concentrations of serum IgG to be achieved, and more liberal use of antibiotics. [from GeneReviews]

IGHD3 is characterized by agammaglobulinemia and markedly reduced numbers of B cells, short stature, delayed bone age, and good response to treatment with growth hormone (summary by Conley et al., 1991). For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400. [from OMIM]

Proteasome-associated autoinflammatory syndrome-1 (PRAAS1) is an autosomal recessive disorder characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12; PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21; PRAAS4 (619183), caused by mutation in the PSMG2 gene (609702) on chromosome 18p11; PRAAS5 (619175), caused by mutation in the PSMB10 gene (176847) on chromosome 16q22; and PRAAS6 (620796), caused by mutation in the PSMB9 gene (177045) on chromosome 6p21. [from OMIM]

Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230). [from OMIM]

Behçet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behçet disease result from widespread inflammation of blood vessels (vasculitis). This inflammation most commonly affects small blood vessels in the mouth, genitals, skin, and eyes.

Painful mouth sores called aphthous ulcers are usually the first sign of Behçet disease. These sores can occur on the lips, tongue, inside the cheeks, the roof of the mouth, the throat, and the tonsils. The ulcers look like common canker sores, and they typically heal within one to two weeks. About 75 percent of all people with Behçet disease develop similar ulcers on the genitals. These ulcers occur most frequently on the scrotum in men and on the labia in women.

Behçet disease can also cause painful bumps and sores on the skin. Most affected individuals develop pus-filled bumps that resemble acne. These bumps can occur anywhere on the body. Some affected people also have red, tender nodules called erythema nodosum. These nodules usually develop on the legs but can also occur on the arms, face, and neck.

An inflammation of the eye called uveitis is found in more than half of people with Behçet disease. Eye problems are more common in younger people with the disease and affect men more often than women. Uveitis can result in blurry vision and an extreme sensitivity to light (photophobia). Rarely, inflammation can also cause eye pain and redness. If untreated, the eye problems associated with Behçet disease can lead to blindness.

Joint involvement is also common in Behçet disease. Often this affects one joint at a time, with each affected joint becoming swollen and painful and then getting better.

Less commonly, Behçet disease can affect the brain and spinal cord (central nervous system), gastrointestinal tract, large blood vessels, heart, lungs, and kidneys. Central nervous system abnormalities can lead to headaches, confusion, personality changes, memory loss, impaired speech, and problems with balance and movement. Involvement of the gastrointestinal tract can lead to a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be life-threatening.

The signs and symptoms of Behçet disease usually begin in a person's twenties or thirties, although they can appear at any age. Some affected people have relatively mild symptoms that are limited to sores in the mouth and on the genitals. Others have more severe symptoms affecting various parts of the body, including the eyes and the vital organs. The features of Behçet disease typically come and go over a period of months or years. In most affected individuals, the health problems associated with this disorder improve with age. [from MedlinePlus Genetics]

Systemic autoinflammatory disease with vasculitis (SAIDV) is an autosomal dominant disorder that manifests soon after birth with features such as purpuric skin rash, fever, hepatosplenomegaly, and elevated C-reactive protein (CRP; 123260). Laboratory studies may show leukocytosis, thrombocytopenia, and autoantibodies. A subset of patients develop progressive liver involvement that may result in fibrosis. Other systemic features, such as periorbital edema, conjunctivitis, infections, abdominal pain, and arthralgia are usually observed. Mutations occur de novo. De Jesus et al. (2023) referred to this disorder as LAVLI (LYN kinase-associated vasculopathy and liver fibrosis). [from OMIM]

The presence of inflammation of the epididymis. [from HPO]