Recent advances in understanding and managing adenosine deaminase and purine nucleoside phosphorylase deficiencies

Curr Opin Allergy Clin Immunol. 2013 Dec;13(6):630-8. doi: 10.1097/ACI.0000000000000006.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Deaminase / deficiency*
  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / immunology
  • Adenosine Deaminase / therapeutic use
  • Agammaglobulinemia* / drug therapy
  • Agammaglobulinemia* / enzymology
  • Agammaglobulinemia* / genetics
  • Agammaglobulinemia* / immunology
  • Agammaglobulinemia* / mortality
  • Animals
  • Enzyme Replacement Therapy*
  • Humans
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Macrophages, Alveolar / enzymology
  • Macrophages, Alveolar / immunology
  • Primary Immunodeficiency Diseases
  • Purine-Nucleoside Phosphorylase / deficiency*
  • Purine-Nucleoside Phosphorylase / genetics
  • Purine-Nucleoside Phosphorylase / immunology
  • Purine-Nucleoside Phosphorylase / therapeutic use
  • Purine-Pyrimidine Metabolism, Inborn Errors* / diet therapy
  • Purine-Pyrimidine Metabolism, Inborn Errors* / enzymology
  • Purine-Pyrimidine Metabolism, Inborn Errors* / genetics
  • Purine-Pyrimidine Metabolism, Inborn Errors* / immunology
  • Purine-Pyrimidine Metabolism, Inborn Errors* / mortality
  • Purines / immunology
  • Purines / metabolism
  • Purkinje Cells / enzymology
  • Purkinje Cells / immunology
  • Severe Combined Immunodeficiency* / drug therapy
  • Severe Combined Immunodeficiency* / enzymology
  • Severe Combined Immunodeficiency* / genetics
  • Severe Combined Immunodeficiency* / immunology
  • Severe Combined Immunodeficiency* / mortality
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology

Substances

  • Purines
  • Purine-Nucleoside Phosphorylase
  • ADA protein, human
  • Adenosine Deaminase

Supplementary concepts

  • Purine Nucleoside Phosphorylase Deficiency
  • Severe combined immunodeficiency due to adenosine deaminase deficiency