Recessive Familial Erythrocytosis: Aspects of Marrow Regulation in Two Families

Studies of marrow regulation were carried out in two families with recessively expressed erythrocytosis. The erythrocytosis in the affected individuals was associated with increased erythropoietin (ESF) production. However, hormone production was uninfluenced by alterations in the O₂ carrying capacity of the blood when the hematocrit was lowered acutely by phlebotomy. Hemoglobin and red cell function (p50; 2, 3-diphosphoglycerate) in the affected, as well as the unaffected, family members were normal. Renal arteriography revealed no mass lesions and no anatomic abnormalities of the renal macro- or microvasculature. Antisera capable of neutralizing the biological activity of normal human ESF completely inhibited the erythropoietic activity in the serum and urine of those studied. Since increased production of ESF occurred in the absence of recognizable physiologic requirements and since the normal reciprocal relationship between O₂ delivery and hormone production was absent, the most likely explanation for this clinical constellation is a cellular defect in the regulation of production of ESF or of its precursor substances.