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The excretion of position isomers of penta- and hexa-carboxylated porphyrins type III in the urine in a case of congenital erythropoietic porphyria characterized by the excretion of large amounts of penta-, hexa- and hepta-carboxylated porphyrins type III together with isocoproporphyrins both in the urine and faeces, and a simple method for the synthesis and separation of such position isomers has been described. The implications of the finding of position isomers type III have been discussed and it is suggested that the decarboxylation of uroporphyrinogen III both in the present case and under physiological conditions is a random process.

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. Beta-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 prophyrin 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 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.

A 5-year-old girl with the classical clinical features of congenital erythropoietic porphyria (CEP) is described. Different types of CEP are discussed based on varying excretion patterns of porphyrins.

The excretion of position isomers of type III porphyrins, not only in porphyric disorders in which the enzymatic decarboxylation of uroporphyrinogen III to coproporphyrinogen III is known to or suspected to play a role, but also in normal man and in conditions like erythropoietic protoporphyria and lead-intoxication, in which no such changes have ever been reported, or would be expected for theoretical reasons, has been described. The implications of these and other findings have been discussed and it is suggested that the enzymatic decarboxylation of uroporphyrinogen III to coproporphyrinogen III is normally a random process. It is, however, not excluded that one of the many routes which could be followed might be energetically more favourable than the others and that most of the coproporphyrinogen III which is formed under physiological conditions might be formed via such a 'prefered' pathway.

The urinary excretion of porphyrins in two cases of porphyria cutanea tarda (PCT) has been followed during a period in which various treatments have been tried. In one patient pyridoxal-5-phosphate (P-5-P) injections lead to a dramatic increase in porphyrin excretion. In another P-5-P treatment was followed by a significant decrease in porphyrin excretion. p-Aminobenzoic acid (PABA) apparently had no effect on porphyrin excretion, while repeated phlebotomies had the expected effect. In both patients all variations in the total amount of porphyrins excreted were almost exclusively due to the variations in the amounts of heptacarboxylic porphyrin type III and uroporphyrin I. A secondary finding was an increase in hexa- and penta-carboxylic porphyrins type III without a concomitant increase in coproporphyrin III.