Immundeficiency 7 D81.4

Immunodeficiency-7 is an autosomal recessive immunodeficiency syndrome (see also Primary Immunodeficiencies) characterized by the presence 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 tests show elevated serum IgE, low numbers of T cells, low TCR-alpha/beta cells, and elevated TCR-gamma/del11ta cells.

If left untreated, the disease often leads to death in early childhood.

Morgan et al (2011) reported on two unrelated children from consanguineous families of Pakistani origin with primary immunodeficiency disease. They presented at 15 and 6 months of age, respectively, with recurrent respiratory infections, otitis media, candidiasis, diarrhea, and failure to thrive. One child showed a clear predisposition to herpesvirus infections requiring long-term antiviral therapy and intravenous immunoglobulin, whereas the other child had only one uneventful varicella event at 6 years of age. Both children had additional features of immune dysregulation, including hypereosinophilia, low titers of antinuclear and other autoantibodies, vitiligo, eczema, and alopecia areata. Other features included lymphadenopathy and hepatosplenomegaly. Humoral immunity appeared normal.

Flow cytometric analysis showed the presence of CD3+ T cells, but they uniformly expressed TCR-gamma/delta and little or no TCR-alpha/beta. Therapy: Both children received bone marrow transplantation.

Rawat et al (2021) reported on an unrelated Indian family in which three siblings had a fatal complex immunologic disorder. Features included recurrent lower respiratory tract infections with crepitations, bronchiectasis, pallor, syndactyly, generalized lymphadenopathy, and hepatosplenomegaly. The two older siblings had verrucae vulgares since infancy. Laboratory tests revealed high IgE levels, elevated IgA levels, low CD4+ and CD8+ T cells, decreased TCR-alpha/beta T cells, and markedly increased proportions of gamma/delta T cells. The mutant alpha chain does not form a normal complex with the TCR-beta chain. The oldest sibling died of severe pneumonia and cor pulmonale; the middle, of pulmonary complications. The youngest child had similar features but additionally developed mature cell EBV-positive B-cell lymphoma, which eventually led to death.

1. Morgan N V et al (2011) Mutation in the TCR-alpha subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCR-alpha/beta+ T cells. J Clin Invest 121: 695-702.
2. Rawat A et al.(2021) Skewed TCR alpha, but not beta, gene rearrangements and lymphoma associated with a pathogenic TRAC variant. J Clin Immun 41: 1395-1399.