Recent advances in understanding and managing adenosine deaminase and purine nucleoside phosphorylase deficienciesGrunebaum, Eyal; Cohen, Amos; Roifman, Chaim M.Current Opinion in Allergy and Clinical Immunology: December 2013 - Volume 13 - Issue 6 - p 630–638 doi: 10.1097/ACI.0000000000000006 PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Ramsay L. Fuleihan and Bruce D. Mazer Abstract Author Information Purpose of the review To review the recent advances in the understanding and management of the immune and nonimmune effects of inherited adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies. Recent findings Abnormal thymocyte development and peripheral T-cell activation in ADA-deficient and PNP-deficient patients cause increased susceptibility to infections and immune dysregulation. The impaired purine homeostasis also damages many other cell types and tissues. Animal studies suggest that defects in surfactant metabolism by alveolar macrophages cause the pulmonary alveolar proteinosis commonly seen in ADA-deficient infants, while toxicity of purine metabolites to cerebellar Purkinje cells may lead to the ataxia frequently observed in PNP deficiency. Patients’ outcome with current treatments including enzyme replacement and stem cell transplantations are inferior to those achieved in most severe immunodeficiency conditions. New strategies, including intracellular enzyme replacement, gene therapy and innovative protocols for stem cell transplantations hold great promise for improved outcomes in ADA and PNP deficiency. Moreover, newborn screening and early diagnosis will allow prompt application of these novel treatment strategies, further improving survival and reducing morbidity. Summary Better understanding of the complex immune and nonimmune effects of ADA and PNP deficiency holds great promise for improved patients’ outcome. Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Correspondence to Dr Eyal Grunebaum, Head, Division of Immunology and Allergy, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada. Tel: +1 416 8138625; fax: +1 416 8138624; e-mail: firstname.lastname@example.org Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.