Recent advances in understanding and managing adenosine deaminase and purine nucleoside phosphorylase deficiencies
- 1 December 2013
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Allergy and Clinical Immunology
- Vol. 13 (6), 630-638
- https://doi.org/10.1097/aci.0000000000000006
Abstract
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. 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. Better understanding of the complex immune and nonimmune effects of ADA and PNP deficiency holds great promise for improved patients' outcome.Keywords
This publication has 71 references indexed in Scilit:
- Purine Nucleoside Phosphorylase Deficiency: A Mutation UpdateNucleosides, Nucleotides and Nucleic Acids, 2011
- Clinical and immunological manifestations of patients with atypical severe combined immunodeficiencyClinical Immunology, 2011
- Progressive multifocal leukoencephalopathy in purine nucleoside phosphorylase deficiencyBrain & Development, 2007
- Carrier Frequency of a Nonsense Mutation in the Adenosine Deaminase (ADA) Gene Implies a High Incidence of ADA‐deficient Severe Combined Immunodeficiency (SCID) in Somalia and a Single, Common Haplotype Indicates Common AncestryAnnals of Human Genetics, 2006
- Mitochondrial Basis for Immune DeficiencyThe Journal of Experimental Medicine, 2000
- Protection by Various Deoxynucleosides against Deoxyadenosine-Induced DNA Damage in Adenosine Deaminase-Inactivated LymphocytesMolecular Genetics and Metabolism, 1999
- Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombinationJCI Insight, 1999
- Deoxyguanosine Triphosphate as a Possible Toxic Metabolite in the Immunodeficiency Associated with Purine Nucleoside Phosphorylase DeficiencyJCI Insight, 1978
- NUCLEOSIDE-PHOSPHORYLASE DEFICIENCY IN A CHILD WITH SEVERELY DEFECTIVE T-CELL IMMUNITY AND NORMAL B-CELL IMMUNITYThe Lancet, 1975
- ADENOSINE-DEAMINASE DEFICIENCY IN TWO PATIENTS WITH SEVERELY IMPAIRED CELLULAR IMMUNITYThe Lancet, 1972