organisms. These infants have a clinical course featuring recurrent infections 
with all classes of microorganisms involving the skin, central nervous system, 
sinopul monary and gastrointestinal tracts. The affected children usually fail 
to thrive and have chronic diarrhea and malabsorption, skin rashes, and a high 
Incidence of lymphoma. The disease is uniformly lethal with death often by 1-2 
years of age. SCID can occur In both autosomal recessive and X-l inked forms 
with the biochemical basis for most cases unknown. ADA( -) SCID Is inherited as 
an autosomal recessive. The heterozygote parents are diagnosable because they 
have approximately 50? of the normal concentration of ADA in their cells. 
Adenosine deaminase catalyzes the conversion of adenosine (Ado) and 
deoxyadenosine (dAdo) to Inosine and deoxylnosine respectively. In the absence 
of ADA. dAdo accumulates intracel 1 ul arly (as well as extracel 1 ul arly) and 
becomes phosphoryl ated to dATP. a compound normally not detected at high levels 
In mammalian cells. Although the exact mechanism Is still unclear, it Is known 
that severe Immune deficiency Is a direct consequence of the deficiency of ADA. 
The production of dATP from dAdo Is Involved in the cellular toxicity observed. 
Although ADA Is deficient In all the cells of the body. T cells have the 
highest concentrations of any cell In the body of the enzymes which 
phosphoryl ate dAdo to dATP. This probably accounts for the observation that 
Immunodeficiency is the prominent pathological consequence of ADA deficiency. 
Furthermore, when deoxycoformycin (a potent Inhibitor of ADA) is used in the 
treatment of acute lymphocytic leukemia a similar degree of immune deficiency 
Is seen to develop in the patient. 
The immunologic abnormalities common in ADA( -) SCID include a striking 
depletion of T lymphocytes in all lymphoid organs. The patients are anergic 
and many patients have no detectable T cells in their peripheral blood while a 
few may have up to 30-40? of normal T cell counts. Despite the presence of T 
[9] 
Recombinant DNA Research, Volume 12 
