2 -Deoxy adenosine dATP

The basic cause of the severe immunodeficiency symptoms is uncertain. However, adenosine deaminase also catalyzes hydrolysis of 2 -deoxyadenosine, and in the absence of the enzyme both this compound and its trinucleotide precursor 2 -deoxy-ATP (dATP) accumulate in tissues.312 Ribonucleotide reductase is... 

When two acid molecules condense by elimination of a molecule of water, the product is called an acid anhydride, as can be seen in Figure 12.60. Acid anhydrides are always very reactive, or high-energy, compounds. When deoxy-adenosine monophosphate forms an anhydride with phosphoric acid, we have deoxyadenosine diphosphate (dADP). Of course, if we add an additional phosphate group, we have deoxyadenosine triphosphate (dATP). 

Severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency (ADA) exhibits autosomal recessive inheritance, and may account for up to 209 of cases (l). Accumulation of intracellular toxic deoxynucleotides and/or S-adenosyl homocysteine particularly in T cells, is considered responsible for the severe lymphoid depletion and dysfunction observed in affected children (2). Unlike other forms of SCID, this variety is amenable to enzyme replacement therapy using regular fresh irradiated red blood cell transfusions as the source of enzyme. Another form of therapy suggested from in vitro studies, is the use of deoxycytidine which theoretically would act as a competitive substrate for deoxycytidine kinase, the enzyme considered responsible for the intracellular accumulation of deoxy-ATP (dATP). This study reports our experience of various treatments in three ADA deficient children. 

---