Immune Defect Due To Absence Of Thymus

Clinical Features

Nezelof et al. (1964) first reported the syndrome of T-cell deficiency with little or no abnormality of gammaglobulin. The possibility of a separate entity distinct from Bruton type agammaglobulinemia (300755), in which the tonsillar system is absent, and from severe combined immunodeficiency (SCID; see, e.g., 300400 and 601457), in which both the thymus and the tonsillar systems are absent, was postulated also by Cooper et al. (1965). In Nezelof syndrome, the defect may be limited to the thymus system which is responsible for cellular immunity. The cases of Allibone et al. (1964) may be examples.

Fulginiti et al. (1966) observed 2 sisters in 1 family and a brother and sister in another family with thymic dysplasia (similar to that seen in Swiss-type agammaglobulinemia), lymphopenia and normal immunoglobulins. Three died before age 2 years of recurrent pseudomonas and monilia infections. The living child displayed impaired delayed hypersensitivity. No skin reactions to mumps, parainfluenza, or monilia antigens were observed. Repeated attempts to produce sensitivity to fluorodinitrobenzene failed and a skin graft from the mother showed no skin rejection. Fireman et al. (1966) reported a case.

Nahmias et al. (1967) observed marked susceptibility to measles with death from giant cell pneumonia. Autopsy showed plasma cells but no small lymphocytes and no thymus. In the black sibship they described, 3 girls and 1 boy were definitely affected and another girl may have been affected. Humoral immunity is normal but cellular immunity is deficient, findings opposite to those of congenital agammaglobulinemia (Kretschmer et al., 1968).

Lawlor et al. (1974) referred to the Nezelof syndrome as the 'syndrome of cellular immunodeficiency with immunoglobulins.' Despite normal or increased levels of one or more of the major immunoglobulin classes, antibody synthesis is impaired.

Rezza et al. (1974) reported a mother and 2 of her 3 children with deficiency in the thymus-dependent immune system. They postulated either a partial defect or precocious involution of the thymus. The children had recurrent herpes labialis and chronic bronchopulmonary infection leading to bronchiectasis and emphysema. Together with the mother, they had lymphopenia and a defect in T-lymphocyte-dependent reactions. The mother, 'though of frail habitus,' had always been healthy and the defect demonstrated in the laboratory was much less severe than that in the children.

Inheritance

Nezelof (1968) presented a pedigree strongly suggestive of autosomal recessive inheritance.