Asymptomatic erythrocyte disorder presenting as increased porphobilinogen deaminase and uroporphyrinogen decarboxylase.

A 23-year-old laboratory assistant who routinely measured erythrocyte porphobilinogen deaminase and uroporphyrinogen decarboxylase tested his own blood. When the results were unexpectedly high, a hematological evaluation was carried out (Table 1). A peripheral blood smear showed anisocytosis, poikilocytes, microspherocytes, elliptocytes, tear-drop forms, and schistocytes. He had jaundice as a neonate, and a borderline hematocrit was noted when he first attempted to donate blood. There was no family history of blood disorders. His ancestry was Irish. Results of a physical examination were normal. The provisional diagnosis was hereditary elliptocytosis; molecular studies of erythrocyte membrane proteins are underway elsewhere. Porphobilinogen deaminase (also known as hydroxymethylbilane synthase and formerly known as uroporphyrinogen I synthase) is known to be increased in patients with clinically significant hemolytic anemias (1). The present case suggests that uroporphyrinogen decarboxylase, another cytosolic enzyme of the heme biosynthetic pathway, is also increased when erythropoiesis is stimulated. Therefore, these erythrocyte enzymes can be sensitive indicators of a relatively benign hemolytic disorder even when the reticulocyte count shows little or no increase. They probably continue to decline with erythrocyte aging even after cells lose the morphologic features of reticulocytes. Heterozygous deficiencies of porphobilinogen deaminase and uroporphyrinogen decarboxylase occur in acute intermittent porphyria and familial porphyria cutanea tarda, respectively (2-4). In most cases of these autosomal dominant disorders, the respective enzyme activity is approximately half-normal in erythrocytes. Erythrocyte uroporphyrinogen decarboxylase is not decreased in patients with the acquired form of porphyria cutanea tarda. Given the substantial effects of increased erythropoiesis on these enzymes in erythTable 1. Hematological values of asymptomatic 23-year-old subject.