Genetic Aspects of Porphyria Cutanea Tarda

Abstract

Porphyria cutanea tarda (PCT) is caused by disruption of heme biosynthesis at the step catalyzed by uroporphyrinogen decarboxylase. The patients present with photosensitive cutaneous lesions, hepatic pathology (including elevated porphyrin levels), and increased excretion of porphyrins. Therapy consists of removing the exacerbating factors of PCT (reduced sunlight exposure, abstinence from alcohol use, decreased estrogen exposure, and treatment for viral infections), decreasing body iron stores (by therapeutic phlebotomy or by the use of the new orally active iron chelators), and, in some instances, the use of low-dose antimalarials. Recent advances in genetics and genomics have allowed DNA testing for porphyria cutanea tarda and are likely to be instrumental in developing improved, gene-based treatments and in finding genetic loci (in addition to uroporphyrinogen decarboxylase) involved in the clinical expression of this disease.

Lésions sclérodermiformes dans la porphyrie cutanée tardive : six observations

“…La maladie dérive d'une dysfonction enzymatique dans le catabolisme de l'uroporphyrinogène ayant comme consé-quence l'accumulation des porphyrines, notamment dans la peau et le foie. Deux formes de PCT sont décrites : la forme sporadique, la plus fréquente (80 % des cas) avec un déficit hépatique en uroporphyrinogène décarboxylase (URO-D) et la forme familiale, liée à une mutation autosomique dominante du gène de l'URO-D, dans laquelle le déficit enzymatique concerne tous les tissus [1,2]. Les signes cardinaux de la PCT sont par ordre de fréquence : la fragilité cutanée, les bulles du dos des mains, l'hypertrichose malaire et périorbitaire, l'hyperpigmentation, la photosensibilité et les grains de milium, avec une localisation préférentielle aux mains et au visage [3,4].…”

Porphyria cutanea tarda: an intriguing genetic disease and marker

“…Porphyria cutanea tarda, the most common porphyria worldwide, has a global prevalence of one per 10,000 people with a nearly equal sex ratio . Clinical manifestations often first present during middle age, hence the inclusions of the word “tarda” in the conditions name . Prevalence of PCT is variable throughout the world.…”

“…Prevalence of PCT is variable throughout the world. In the United States, one in 25,000 is affected, while in the Czech Republic and Slovakia the prevalence is one in 5000, and in Norway the prevalence is one in 100,000 inhabitants …”

Zebrafish as a Developmental Model Organism for Pediatric Research

“…For example, a mutant fish identified in the original Nusslein-Volhard screen with hematopoetic defects was mapped by our laboratory to the uroporphyrinogen decarboxylase (UROD) gene (19,20). UROD is involved in human porphyria cutanea tarda and hepatoerythropoietic porphyria (21). These syndromes present as sensitivity to sun exposure, including blistering, scarring, and liver problems.…”