THE EFFECT OF VARIOUS THERAPEUTIC TRIALS ON THE PORPHYRIN EXCRETION IN A CASE OF CONGENITAL ERYTHROPOIETIC PORPHYRIA

ABSTRACT: Eriksen, L. and Seip, M. (Institute of Physiology, University of Oslo, and Department of Pediatrics, University Hospital, Oslo, Norway). The effect of various therapeutic trials on the porphyrin excretion in a case of congenital erythropoietic porphyria. Acta Paediatr Scand 64:287, 1975.–A patient with a biochemically "new" type of congenital erythropoietic porphyria has been studied under various therapeutic trials. Splenectomy had no demonstrable effect on porphyrin excretion or clinical picture. Vitamin E caused a moderate fall in porphyrin excretion, however, there was no significant improvement in light tolerance and tendency to hemolysis. β-carotene reduced skin photosensitivity appreciably, while total porphyrin excretion remained unchanged and the tendency to develop hemolytic anemia showed only slight improvement. Red cell transfusion caused a rapid, dramatic fall in porphyrin excretion (in 4–5 days) and a transient increase in light tolerance, while the distribution of the different porphyrins excreted remained unchanged. These observations indicate that all or nearly all the abnormal porphyrins excreted are of erythropoietic origin, and that the overwhelming part of the porphyrins originate from an abnormal population of shortlived red cells. Findings on fluorescence microscopy of blood and bone marrow support this view. Meticulous protection against light of the shorter wavelengths caused a similar rise in hemoglobin level as produced by red cell transfusion, however, in this instance the total excretion of porphyrins did not fall. It is suggested that the inhibitory effect of transfusion on erythropoiesis (and thereby porphyrin excretion) might be due partly to a depression of erythropoietin formation, partly to the presence of an erythropoiesis inhibiting factor (chalone) in the transfused red cells.     

Different Substrate Specificities of Plasma Lecithin: Cholesterol Acyl Transferase in Fish Eye Disease and Tangier Disease

ABSTRACT Esterification of plasma free cholesterol is mediated by lecithin: cholesterol acyl transferase (LCAT). The free cholesterol of plasma high density lipoproteins (HDL) is considered to be the preferred substrate for LCAT. It therefore appeared as a paradox that plasma cholesterol esterification, both in vivo and in vitro, is normal in fish eye disease and Tangier disease, two familial conditions with extremely low plasma HDL levels. Fish eye disease plasma, however, was shown to have LCAT activity primarily acting on combined very low (VLDL) and low (LDL) density lipoproteins, denominated β-LCAT, while it lacked LCAT activity esterifying HDL cholesterol (α-LCAT). Here we show that Tangier plasma, in contrast, has both α- and β-LCAT. Thus, in both fish eye and Tangier diseases it is β-LCAT that explains the apparent normal plasma cholesterol estenfication. We also show that Tangier plasma, having α-LCAT activity, normalizes the low cholesteryl ester content as well as the abnormally small size of fish eye disease HDL particles during incubation.