[Immune deficiencies secondary to enzymopathies]

Immune deficiencies secondary to enzyme deficiencies that affect purine and pyrimidine metabolism account for approximately 50% of severe immune deficiencies inherited as a recessive autosomal trait. Adenosine deaminase (ADA) deficiency is the most common and also the earliest and most severe of these diseases. ADA deficiency is responsible for a severe combined immune deficiency with alymphocytosis and often characteristic bone and cartilage abnormalities. The treatment of choice is transplantation of compatible bone marrow; in cases where this has not been feasible, replacement therapy with the enzyme coupled to polyethylene glycol has yielded promising results. Purine nucleoside phosphorylase (PNP) deficiency is responsible for an isolated T cell defect. Low serum uric acid levels are highly suggestive of PNP deficiency. Bone marrow transplantation is indicated. In both diseases, the immune deficiency is due to the toxic effect of purine deoxynucleosides on lymphoid cells. Enzyme deficiencies that directly or indirectly affect pyrimidine metabolism (orotate phosphoribosyltransferase and methionine synthase deficiencies) are exceedingly rare and only inconsistently produce an immune defect (involving T cells).