Studies on erythropoietic protoporphyria

Abstract

Erythropoietic protoporphyria, first reported in 1961, is an inherited metabolic disorder, characterized by cutaneous photosensitivity, normal urinary porphyrin levels and increased protoporphyrin IX concentrations in erythrocytes, plasma and faeces. Diagnosisin photosensitive patients is made by observing fluorescent erythrocytes under ultraviolet light microscopy or by quantitating erythrocyte protoporphyrin. This paper reportedresults of studies on six patients with this disorder, andon members of two affected families. These family studies provided evidence to support a dominant modeof inheritance, with a variable expressivity of thetrait causing a number of individuals to show no clinical signs of photosensitivity and only mild biochemical abnormalities, namely, small increases in erythrocyte or faecal prophyrin levels. Some of the many unanswered questions regarding erythropoietic protoporphyria were discussed, including the nature of the metabolic defect. It is likely that the accumulation of protoporphyrin is due to overproduction rather than to a block in the pathway of haem synthesis. Proposed studies in this field were outlined. The mechanism by which overproduction could arise from a constitutive operator mutation via increased enzyme synthesis was explained. The possible mechanism of production of the photosensitive skin reaction in erythropoietic protoporphyria was also discussed.