title: Genetic heterogeneity in partial adenosine deaminase deficiency.
abstract: Inherited deficiency of the enzyme adenosine deaminase (ADA) results in a syndrome of severe combined immunodeficiency (SCID). Children with ADA- -SCID lack ADA in all cells and tissues. In contrast, a "partial" deficiency of ADA has been described in six immunologically normal children from four different "families." These children lack ADA in their erythrocytes but retain variable amounts of activity in their lymphoid cells. We have examined ADA activity in lymphoid line cells from four of these children, who are unrelated, for evidence of genetic heterogeneity. One child, who is Caucasian, has an enzyme with increased electrophoretic mobility, a diminished isoelectric point (pI 4.8 vs. Nl = 4.9) and very low activity (2.3 vs. Nl = 82.9 +/- 12.9 nmol/mg protein per min); as a second child has an enzyme with normal electrophoretic mobility but increased isoelectric point (pI = 5.0), markedly diminished heat stability at 56 degrees C (t1/2 = 4.2' vs. Nl = 40') and low activity (12.1); a third has an enzyme with only diminished heat stability (t1/2 = 6.5'), no detectable abnormality in charge and almost normal activity (41.9); while the fourth exhibits only diminished ADA activity (25.0) with no striking qualitative abnormalities. Thus, we have found evidence for three different mutations at the structural locus for ADA in three of these individuals, (a) an acidic, low activity heat stable mutation (b) a basic, somewhat higher activity, heat labile mutation, and (c) a relatively normal activity heat labile mutation. In the fourth, there is as yet no compelling evidence for a mutation at the structural locus for ADA and a mutation at a regulatory locus cannot be excluded.
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D002460:Cell Line; D002648:Child; D004355:Drug Stability; D004592:Electrophoresis, Starch Gel; D005796:Genes; D006358:Hot Temperature; D006801:Humans; D007526:Isoelectric Point; D007527:Isoenzymes / Q000235:genetics; D008214:Lymphocytes / Q000201:enzymology*; D009154:Mutation; D009700:Nucleoside Deaminases / Q000172:deficiency*
chemical_list: D007527:Isoenzymes; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase