To review current breakthroughs in the knowledge and management of hereditary adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies’ immunological and nonimmune consequences. In ADA-deficient and PNP-deficient individuals, abnormal thymocyte formation and peripheral T-cell activation result in increased vulnerability to infections and immunological dysregulation. Purine homeostasis was disrupted in many different cell types and tissues. Animal studies showed that alveolar macrophage abnormalities in surfactant metabolism explained the pulmonary alveolar proteinosis seen in ADA-deficient newborns, whereas purine metabolite toxicity to cerebellar Purkinje cells induced the ataxia seen in PNP deficiency. Patients’ outcomes with existing therapies, such as enzyme replacement and stem cell transplants, were worse than in the majority of severe immunodeficiency diseases. New techniques, such as intracellular enzyme replacement, gene therapy, and novel stem cell transplantation protocols, showed considerable potential for improving ADA and PNP deficient outcomes. Furthermore, newborn screening and early diagnosis allowed these revolutionary treatment techniques to be implemented more quickly, boosting the survival and lowering morbidity.
Improved patient outcomes might be aided by a better knowledge of the complicated immunological and nonimmune implications of ADA and PNP deficiency.
Reference:journals.lww.com/co-allergy/Abstract/2013/12000/Recent_advances_in_understanding_and_managing.7.aspx
