Agammaglobulinaemia.

Abstract

Agammaglobulinaemia is the most common of the primary immunodeficiencies. Three major types can be distinguished: X-linked agammaglobulinaemia, early-onset agammaglobulinaemia and late-onset agammaglobulinaemia. In X-linked agammaglobulinaemia, the molecular defect has been elucidated, and genetic counseling, prenatal diagnosis and carrier detection have become important issues. The pathogenesis of early- and late-onset agammaglobulinaemia is heterogeneous and usually not within the B-cell lineage. Patients with agammaglobulinaemia mainly suffer from infections caused by pneumococci or encapsulated Haemophilus influenzae located in the respiratory tract, paranasal sinuses, ears and meninges. Other prominent infections are Campylobacter jejuni bacteraemia and Giardia lamblia infection of the intestine. Among the more rare infections are those caused by Ureaplasma and Mycoplasma hominis. There is quite a number of non-infectious abnormalities which bother agammaglobulinaemic patients, especially those with late-onset agammaglobulinaemia. Of these, gastric carcinoma and intestinal lymphoma in late-onset agammaglobulinaemia and colorectal cancer in X-linked agammaglobulinaemia are the most dramatic. Life-threatening bacterial infections can largely be prevented by immunoglobulin substitution, even at relatively low dosages. However, insufficient immunoglobulin substitution is associated with recurrent airway infection and cumulative damage to the respiratory tract. for adequate substitution, efficacieous and safe intravenous immunoglobulin preparations are available. For selected patients (children, adults with poor venous access, and those experiencing side-effects on intravenous immunoglobulin), 16% immunoglobulin can be given by the subcutaneous route. With optimal substitution and--in the case of infection--adequate antimicrobial treatment, these patients have a good prognosis.