Scientific Article about Porphyria

Read the full article at http://bloodjournal.hematologylibrary.org/content/95/5/1565.long , or get our summary of this article below!

Summary

Porphyria cutanea tarda (PCT) is the most prevalent subtype of porphyria in humans, with prevalence ranging from 1 in 5000 to 25000. Clinically, PCT is recognized by photosensitive, fragile skin which blisters with high exposure to sunlight. The disorder is caused by an inherited mutation in the UROD gene, and sometimes in the HFE gene.

UROD (Uroporphyrinogen III decarboxylase)  is coded by the human UROD gene and is an enzyme in the heme biosynthetic pathway. Mutation in the UROD gene greatly affects heme production and leads to PCT.

On the other hand, the HFE (Human hemochromatosis protein) helps to regulate the interaction of the transferrin receptor with transferrin, hence regulating iron absorption from digestive tract. Defect in the HFE gene leads increased chances of developing PCT.

Although PCT is caused by gene mutations, there are also other risk factors for the development of PCT, such as excess alcohol intake, estrogen exposure and HCV (Hepatitis C Virus) infection. From experiments conducted in this paper, it is shown that mutated HFE gene and HCV infection pose as the greatest risks, while estrogen and alcohol prove to be individual risk factors leading to the development of PCT.

It would not be an understatement to say that pathogenesis of PCT is the result of both genetic and environmental factors. Two genetic factors: mutated UROD gene and mutated HFE gene, along with environmental factors such as excess alcohol consumption, trigger the phenotypic expression of PCT in majority of the cases. Either genetic factor or environmental factor alone is not capable of expressing the PCT phenotype. Many who carry the mutant HFE/UROD allele do not show the phenotype and the proportion of the human population exposed to alcohol, estrogen and HCV infection are far greater than the occurance of PCT. It can be therefore, concluded that as with many other diseases, porphyria cutanea tarda is an interplay of genetic and environmental contributions, of which the link between both contributions remains unknown.