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 pyrimidine-5'-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.

Glutathioneperoxidase activity was measured in blood and cultured fibroblasts from healthy persons of several different

An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6- phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.

Glutathione peroxidase (GSHPx) activity was found to be greatly elevated in members of a family with alpha-thalassemia. Eleven other families with proven alpha-thalassemia were investigated, and all but one subject with hemoglobin H disease had increased red cell GSHPx. Most persons with alpha-thalassemia trait also had increased activity of red cell GSHPx. In contrast, only very modest increases in glutathione peroxidase activity were observed in subjects with various forms of beta-thalassemia.