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.

Hereditary polymorphic light eruption is a form of photosensitivity found in the American Indians of the central plains of Canada and the United States and in the Indians of Central and South America. The disorder has also been called familial actinic prurigo, solar dermatitis, and hydroa aestivale. In northern latitudes, skin lesions appear on exposed areas early in spring, become severe during the summer, and abate in the fall. Usually the disorder appears in childhood with eczematous crusted eruptions on the face and arms. Fissured, crusted exudative cheilitis develops on the lips, especially the lower lip. The dorsum of the hands, the laterodorsal aspects of the forearms, and the lower half of the arms often show excoriated papular and nodular lesions. Children frequently have complicating pyoderma. Adults usually exhibit an erythematous plaquelike eruption on the face and other exposed areas. The disease is more severe in children than in adults. Glomerulonephritis can follow streptococcal pyoderma (summary by Fusaro and Johnson, 1980).

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.

An autosomal recessive condition caused by mutation(s) in the IL10RA gene, encoding interleukin-10 receptor subunit alpha. It is characterized by early-onset chronic relapsing intestinal inflammation.

T-cell immunodeficiency with thymic aplasia (TIDTA) is an autosomal recessive disorder that is often detected at birth through newborn SCID screening with the finding of decreased T-cell receptor excision circles (TRECs). Affected individuals have selective hypo- or aplasia of the thymus, which results in T-cell immunodeficiency due to impaired T-cell development and increased susceptibility to viral infections. The phenotype is similar to T-/B+/NK+ SCID. Some patients may die in childhood; thymus transplantation may be curative (summary by Du et al., 2019).