Haem synthesis in the Diamond-Blackfan syndrome.
The response of bone marrow to erythropoietin (EPO) from five children with the Diamond-Blackfan syndrome, also known as congenital hypoplastic anaemia (CHA), was tested in tissue culture by measurement of haem synthesis. Studies of 13 control marrows indicated that the maximum EPO effect occurred at approximately 70 h incubation using an EPO concentration of 0.2-0.3 units/ml and a nucleated cell concentration of 5 x 10(6) per culture. Under these conditions, haem synthesis was 121% greater in EPO-stimulated than in unstimulated cultures. Patients with CHA with anaemia and diminished marrow erythroids had reduced or absent haem synthesis. In one patient, haem production became normal after a spontaneous remission, and was not inhibited by autologous plasma drawn at the time of diagnosis. Plasma from three patients did not show inhibitory activity when cultured with control marrow. In contrast, plasma from an adult with acquired pure red cell aplasia produced striking inhibition of haem synthesis when cultured with control marrow. We conclude that, in comparison to some cases of the adult acquired condition, CHA is not due to inhibitors or antibodies. When present, erythroid precursors in children with CHA are capable of responding normally to EPO with increased haem synthesis.
D000741:Anemia, Aplastic / Q000097:blood; D001853:Bone Marrow / Q000032:analysis; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004913:Erythrocytes, Abnormal; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D006418:Heme / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D013577:Syndrome
D004921:Erythropoietin; D006418:Heme