Hemolytic anemia due to pyrimidine-5'-nucleotidase deficiency: report of eight cases in six families.

We describe the clinical. hematologic. and biochemical findings in eight patients with pyrimidine-5’-nucleotidase deficiency occurring in six unrelated families. In most cases, a profound lowering of red cell pyrimidine-5’-nucleotidase activity. associated with the characteristic change in the u.v. spectrum brought about by increased levels of pyrimidine nucleotides was observed. One patient had an atypical presentation in that no stippled cells were apparent in the peripheral blood film. and the u.v. spectrum of red cell extracts was normal or nearly so. In addition, the one parent of this patient whose red cells were tested was not pyrimidine-5’-nucleotidase deficient. This patient may be a heterozygote for pyrimidine5’-nucleotidase deficiency with hemolysis due to this or another cause. Several of the patients were found to be mentally retarded, and in one family in which several sibs. two with and one without pyrimidine-5’-nucleotidase deficiency. could be studied. the low IQ values were found only in the enzyme-deficient subjects. A pyrimidine-5’-nucleotidase activity is found in normal fibroblasts and. to the same extent. in the fibroblast of patients with pyrimidine-5’-nucleotidase deficiency. This activity is largely membrane bound. however. and is inhibited by the 5’-nucleotidase inhibitor, a-$-methylene ADP. Accordingly. it appears that fibroblasts are devoid of the type of specific pyrimidine-5’-nucleotidase activity found in normal erythrocytes. We suggest that pyrimidine-5’-nucleotidase deficiency is one of the more common recognized causes of nonspherocytic hemolytic anemia and that in some cases it may produce, in addition to hemolysis, mental retardation.