Challenging beliefs : only a genetic diagnosis of primary immunodeficiency disorders will suffice for some patients, even in a resource-poor setting

Abstract

Genetic testing has become important in the repertoire for the diagnosis of primary immunodeficiencies. More than 350 genetic disorders have been molecularly characterised since the first description of primary immunodeficiencies. Some authorities regard the first description of Bruton agammaglobulinaemia in 1952 as the foundation of this field, whereas others refer to the first description of neutropaenia in 1922 as its origin. Genetic testing for primary immunodeficiencies is important in order to make a definitive diagnosis, to guide definitive treatment, to arrive at a prognosis, to make prenatal genetic diagnoses, for family planning and to evaluate the risk to other family members. Primary immunodeficiencies often present in various ways, with overlapping symptoms. In resource-poor countries, primary immunodeficiency diagnoses and classifications are often based on the availability of a few basic tests with which only a probable diagnosis can be provided. To a large extent, this influences both management and outcome. In this case series, we describe eight patients in whom next-generation sequencing has proved to be of value in making a definitive diagnosis. Such diagnosis has helped practitioners to guide directed therapy, counsel family members appropriately, enable prenatal testing, predict prognosis and explain the symptoms of family members, including carrier mothers. The series also emphasises the value of and the necessity for genetic testing in resource-limited settings.