Porphyrias are uncommon inherited diseases of haem biosynthesis for which the diagnosis and treatment varies in individual countries. Despite the existence of guidelines recommended by porphyria experts concerning the diagnosis and management of the acute porphyrias, and of specialist centres in most European countries, many clinicians still do not apply these guidelines. The European Porphyia Initiative (EPI) network was formed in 2001 in order to compare experience among countries to attempt to develop a common approach to the management of the porphyrias, particularly concerning recommendation of safe and unsafe drugs, and to facilitate international collaborative clinical and biological research. The main achievements of EPI during this period have been:
•Drafting and agreeing to consensus protocols for the diagnosis and management of acute hepatic porphyrias
•Creation of a multilingual website, particularly focusing on guidelines for common prescribing problems in acute porphyria and on providing information for patients that is now available in 10 languages:
www.porphyria-europe.org.
EPI’s current objectives are to develop the EPI platform, expand to new countries, extend to non-acute porphyrias and design European research and clinical trials in porphyria. The project will focus on:
1.Setting up a European laboratory external quality assurance scheme (EQAS) for biochemical and molecular investigations and theirinterpretation
2.Establishing a consensus drug list in collaboration with the Nordic porphyria network
3.Improving patient counseling
4.Developing large multi-centre, multi-national research projects. Due to the rarity of the porphyrias, it would be very difficult for any one country to provide this data with a sufficient number of patients and within a
reasonable timescale. The progress achieved will facilitate improvements in the treatment and development of new therapeutic strategies. It
will set a pattern for establishing, and subsequently harmonising, between countries best clinical practice for a rare but important group of diseases, and will help to develop the optimal therapy and ensure its cost effectiveness.
Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by partial ferrochelatase deficiency, resulting in protoporphyrin overproduction which is responsible for painful skin photosensitivity. Chronic liver disease is the most severe complication of EPP, requiring liver transplantation in some patients. Data from a
mouse model suggest that cytotoxic bile formation with high concentrations of bile salts and protoporphyrin may cause biliary fibrosis by damaging bile duct epithelium. In humans, cholestasis is a result of intracellular and canalicular precipitation of protoporphyrin. To limit liver damage two strategies may be considered: the first is to reduce protoporphyrin production and the second is to enhance protoporphyrin excretion. Bile salts are known to increase protoporphyrin excretion via the bile, while heme arginate is used to decrease the production of porphyrins in acute attacks of hepatic porphyrias. The Griseofulvin-induced protoporphyria mouse model has been used to study several aspects of human protoporphyria including the effects of bile salts. However,
the best EPP animal model is an ethylnitrosourea-induced point mutation with fully recessive transmission, named ferrochelatase deficiency (Fech
m1Pas). Here we investigate the effect of early ursodesoxycholic acid (UDCA) administration and heme-arginate injections on the ferrochelatase deficient EPP mouse model. In this model UDCA administration and heme-arginate injections do not improve the protoporphyric condition of
Fechm1Pas/Fechm1Pas mice.