Genetic Heterogeneity in Partial Adenosine Deaminase Deficiency

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 de-scribed in six immunologically normal children from four different "families. " These children lack ADA in their erythrocytes but retain variable amounts of ac-tivity 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 electro-phoretic mobility, a diminished isoelectric point (pl 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 mo-bility but increased isoelectric point (pI = 5.0), mark-edly diminished heat stability at 56°C (tl/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 dimin-ished 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 Received for publication 19 May 1982 and in revisedfor