Congenital erythropoietic porphyria, diminished activity of uroporphyrinogen decarboxylase and dyserythropoiesis

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A 51-yr-old white male with congenital erythropoietic porphyria (Giinther's Disease) is described. The disease was first manifested in infancy and mutilating cutaneous photosensitivity eventually developed. The source of excess porphyrin production was a markedly dyserythropoietic bone marrow. The dyserythropoietic changes were most marked in the orthochromic and polychromatophilic normoblasts, and these cells demonstrated a red-orange nuclear fluorescence. The morphological features of the dyserythropoietic cells, studied with light and electron microscopy, were identical to those found in congenital dyserythropoietic anemia type I and are similar to those described in other patients with congenital erythropoietic porphyria. The red-orange nuclear fluorescence was the only feature not usually associated with congenital dyserythropoietic anemia type I. Massive porphyrinuria was present, but the pattern of porphyrin excretion was atypical for congenital erythropoietic porphyria. Hepta carboxyl (7-COOH) porphyrin was the major urine porphyrin, and there was also a large amount of uroporphyrin present. Both were predominantly of the isomer III type. Erythrocyte uroporphyrinogen III cosynthase activity was not subnormal, but uroporphyrinogen decarboxylase activity was 50% of control values. A family study revealed other relatives with the same degree of subnormal erythrocyte uroporphyrinogen decarboxylase activity, but none with congenital erythropoietic porphyria or anemia. This is the first reported case of congenital erythropoietic porphyria associated with deficient activity of uroporphyrinogen decarboxylase, and it suggests that congenital erythropoietic porphyria may be a syndrome rather than a disease due to a specific enzymic defect. The family study in this case suggested that two defects may be required for clinical expression of the porphyria. One is an enzymic defect in the heme biosynthetic pathway and the other is dyserythropoietic anemia, indistinguishable on morphological grounds from congenital dyserythropoietic anemia type I. The morphological changes do not appear to be a consequence of the heme biosynthetic defect.