title: Inheritance in protoporphyria. Comparison of haem synthetase activity in skin fibroblasts with clinical features.
abstract: The activity of haem synthetase, the enzyme which chelates iron to protoporphyrin to form haem, was measured in cultured skin fibroblasts of children with protoporphyria and their parents from three families. In each family, one parent had deficient haem synthetase activity (3-0-11-1 pmol protohaem formed/mg protein/h) when compared to values in eight non-porphyric controls (means 24-9, range 13-7-51-5). The level of activity in the three parents was similar to that in their affected children. In two families the parent with deficient activity was also thought to be the carrier of the abnormal gene, as judged from a history of photosensitivity and analysis of erythrocyte protoporphyrin concentrations, but in the third family the pattern of inheritance could not be determined from these criteria. The activity of delta-aminolaevulinic acid synthetase was normal in cultured fibroblasts from the protoporphyric children and their parents, excluding a generalised defect in haem-pathway enzymes. These results support the premise that deficient haem synthetase activity, inherited in an autosomal dominant patter, is the primary defect in protoporphyria.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001722:Birth Order; D002648:Child; D004912:Erythrocytes / Q000032:analysis; D005243:Feces / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007501:Iron; D008190:Lyases / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011164:Porphyrias / Q000201:enzymology / Q000235:genetics*; D011166:Porphyrins; D011524:Protoporphyrins / Q000032:analysis; D012867:Skin / Q000166:cytology
chemical_list: D011166:Porphyrins; D011524:Protoporphyrins; D007501:Iron; D008190:Lyases