A 3-month-old male infant is brought to the physician because of recurrent viral infections and rashes over his trunk. Lymph nodes are difficult to detect on physical examination; imaging studies indicate the lack of a thymus. Urine deoxyadenosine concentration is 100 times greater than normal. A peripheral blood smear shows a marked decrease in both mature B and T lymphocytes. A deficiency of which of the following enzymes is most likely in this patient?
A. Adenine phosphoribosyltransferase
B. Adenosine deaminase
C. Adenosine kinase
D. Adenylosuccinate synthetase
E. Hypoxanthine-guanine phosphoribosyltransferase
F. Ribonucleotide reductase
Correct answer: B. Adenosine deaminase – ADA deficiency is due to a lack of the enzyme adenosine deaminase. This deficiency results in an accumulation of deoxyadenosine, which, in turn, leads to:
(1) a build up of dATP in all cells, which inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are highly susceptible to this condition.
(2) an increase in S-adenosylhomocysteine since the enzyme adenosine deaminase is important in the purine salvage pathway; both substances are toxic to immature lymphocytes, which thus fail to mature.
Because T cells undergo proliferation and development in the thymus, affected individuals typically have a small, underdeveloped thymus. As a result, the immune system is severely compromised or completely lacking.