CORRELATIONS BETWEEN PURINE LEVELS, CLINICAL AND.IMMUNOLOGICAL STATUS IN ADA DEFICIENCY: 192

Abstract

Nine cases of adenosine deaminase (ADA) deficiency have been found amongst fifty infants investigated for immunodeficiency. Prenatal diagnosis identified a further two affected foetuses in six pregnancies at risk. Absence of ADA activity and high dATP levels in foetal blood,with low lymphoid cell numbers and few T-cells, indicated early intrauterine onset.High dATP levels, accompanied by varying degrees of ATP depletion were also found in the red cells of the nine infants. Two late presenters had normal ATP levels, normal lymphocyte numbers and immunoglobulin levels, with some detectable ADA in mononuclear cells (PBMs). dATP was found in PBMs in only one case where heparinised blood contaminated with platelets was used. The novel finding in the two latest cases was the presence of ATP depletion accompanied by dATP accumulation in the platelets but not PBMs from defibrinated blood. This explains the earlier results and questions the possible significance for the immune response.Deoxyadenosine was found in the urine in all cases.S-adenosylhomocysteine was not; adenosine was identified in some. The results suggest that the degree of ATP depletion may reflect the clinical status most closely,but that any therapeutic approaches are likely to be ineffective because of the early toxicity to T-lymphocyte precursors.