The different types of porphyria in denmark and the importance of family studies

Abstract

1. 1. During 25 yr we have in Denmark registered 126 cases of porphyria cutanea tarda (PCT), 147 cases of acute intermittent porphyria (AIP), 32 of mixed- or variegate-porphyria (VP), 10 of hereditary coproporphyria (HCP), and 34 cases of erythropoietic protoporphyria (EPP). Further, systematic family studies were performed, and about 1600 relatives of patients suffering from hepatic porphyria —i.e. all who were willing to cooperate—were subjected to analysis of urine (porphyrin, PBG and ALA) and feces (porphyrin). Before 1950 AIP was most common, but after 1970 PCT became the most frequent form as is the case also in other European countries; thus Kordač in Prague (1979, personal communication) has 600 cases under treatment. HCP is relatively common in Denmark and usually mild or latent. VP occurs as “mixed porphyria”; the South African type with increased fecal protoporphyrin in all carriers is not found in Denmark. Our results suggest a variation from family to family of the gene penetrance level, as expressed by the number and severity of the manifest cases and the level of the excretion of metabolites in the carriers. 2. 2. A study of a previously published big family (Thiele & With, 1964) is now in progress. This family comprises one manifest case and over hundred relatives with normal excretion in most and only a slightly increased metabolite level in a few. In this study erythrocyte urogensyntase (UPG-S) was included and found normal in most of the relatives. A certain correlation between high gene penetrance and low levels of UPG-S in erythrocytes was found. 3. 3. Our studies on UPG-S comprised 67 normals, 27 porphyries and 91 relatives from 16 different families with AIP and were measured both with fluorimetry and spectrophotometry with uroporphyrin as standard. Previous findings were largely confirmed with 15 nmol/ml erythrocytes/hr as discrimination value, but the overlap between normals and porphyries was considerably greater with spectrophotometry than with fluorimetry.