Inheritance in protoporphyria. Comparison of haem synthetase activity in skin fibroblasts with clinical features
Bloomer, J.R.; Bonkowsky, H.L.; Ebert, P.S.; Mahoney, M.J.
Lancet 2(7979): 226-228
1976
ISSN/ISBN: 0140-6736 PMID: 59242 Document Number: 98621
The activity of heme synthetase, the enzyme which chelates Fe to protoporphyrin to form heme, was measured in cultured skin fibroblasts of children with protoporphyria and their parents from 3 families. In each family, 1 parent had deficient heme synthetase activity (3.O-11.1 pmol protoheme formed/mg protein per h) when compared to values in 8 non-porphyric controls (mean 24.9, range 13.7-51.5). The level of activity in the 3 parents was similar to that in their affected children. In 2 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 3rd family the pattern of inheritance could not be determined from these criteria. The activity of .delta.-aminolevulinic acid synthetase was normal in cultured fibroblasts from the protoporphyric children and their parents, excluding a generalized defect in heme pathway enzymes. Deficient heme synthetase activity, inherited in an autosomal dominant pattern, was the primary defect in protoporphyria.