ADA Deficiency - The First Described Genetic Defect Causing PID
The serendipitous discovery of adenosine deaminase (ADA) deficiency in 1972 preceded by two decades the identification of gene defects in other forms of severe combined immune deficiency (SCID). During that interval, a great deal was accomplished: with knowledge of the underlying enzyme deficiency came a biochemical test for diagnosing ADA-deficient patients. The metabolic consequences of ADA deficiency were determined, the biochemical mechanisms by which ADA substrates and metabolites cause disease were defined and the close relationship of genotype to phenotype became apparent. A novel method of enzyme replacement for ADA deficiency was tested and approved, and the first in human trial of gene therapy was initiated in patients with ADA deficiency.
