Adenosine deaminase deficiency and immunodeficiencies.
Severe Combined Immunodeficiency (SCID) is a fatal disorder of infancy in which patients exhibit profound defects of both cellular and humoral immune function. Approximately 50% of patients with the autosomal recessive form of SCID have a genetically determined deficiency of the purine salvage enzyme adenosine deaminase (ADA). Prenatal diagnosis of SCID-ADA deficiency has been successful and detection of heterozygous carriers has been shown to be feasible. A mutation at the structural locus for ADA has been found in several cases but clinical heterogeneity indicates that genetic heterogeneity at the molecular level is to be expected. In vitro model studies and clinical course suggest that the pathophysiology may involve primarily an inhibition of T-cell maturation with lesser effects on B-cell maturation as well as "self-destruction" of differentiated cells following antigen stimulation. The culprit may be adenosine itself or one of its metabolites such as ATP or cAMP, which are elevated in these patients. Bone marrow transplantation remains the recommended mode of therapy but red cell transfusion may offer an alternative when bone marrow transplantation is not feasible. The finding that deficiency of  the next enzyme in the purine salvage pathway, nucleoside phosphorylase, is also associated with an immune deficiency disorder suggests that integrity of the purine salvage pathway may be crucial for normal differentiation and function of immunocompetent cells in man.
D000241:Adenosine / Q000633:toxicity; D000243:Adenosine Deaminase / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use; D004912:Erythrocytes / Q000201:enzymology; D005808:Genes, Recessive; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D007527:Isoenzymes / Q000172:deficiency; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000172:deficiency*; D010375:Pedigree; D011110:Polymorphism, Genetic; D011296:Prenatal Diagnosis; D012730:Sex Chromosomes
D007527:Isoenzymes; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine