[Widely divergent clinical phenotype of x-linked agammaglobulinemia in two cousins]

Abstract

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency caused by a mutation in the gene encoding Bruton's tyrosine kinase (BTK). The classical presentation of XLA consists of the almost complete absence of B-lymphocytes and immunoglobulins in the peripheral blood leading to severe, mainly bacterial, upper and lower respiratory-tract infections already in early childhood. Irrespective of the kind of BTK-gene mutation the phenotype of XLA can be very diverse. Two 9-year-old cousins with the same BTK-gene mutation illustrate this phenotypical diversity. One boy had a classical presentation and was on maintenance treatment with intravenous immunoglobulins and prophylactic antibiotics to control his infections. Without any prophylactic treatment, his cousin had no abnormal infectious course despite very low B-lymphocyte counts and immunoglobulin levels in the blood. The mechanisms underlying the phenotypical diversity of XLA have not been clarified. Gene polymorphisms affecting the innate immune system may play a role.