Porphyria cutanea tarda:Literally, the lateskinform of porphyria, ageneticphotosensitive (light-sensitive) skindiseasewithonsetin成人life with substances called uroporphyrins in theurinedue to a deficiency ofuroporphyrinogen decarboxylase(UROD), anenzymerequired for thesynthesisof heme (part of hemoglobin, thepigmentin red blood cells that carriesoxygen). The hallmarks ofporphyria cutanea tarda(PCT) are blisters which become ulcerated in areas of the skin exposed to sunlight, especially on the face, ears anddorsum(back) of the hands. The affected areas of skin also tend to be fragile andshowhyperpigmentation(excess pigment) andhypertrichosis(excess hair).
Porphyria cutanea tarda, the most common form of porphyria, comes in twoclinicalfamilialand asporadicform:
- The familial form of porphyria cutanea tarda -- is inherited as anautosomal dominanttraitwith males and females affected in multiple generations. The enzyme UROD is reduced in all tissues.
- The sporadic form of porphyria cutanea tarda -- is more common. The enzyme UROD is only reduced in the liver. It appears sporadically in people with liver disease, as from alcoholism, and from exposure to agents such as estrogens.
Iron overload is frequently present in porphyria cutanea tarda and may be associated with varying degrees of damage of the liver.
A severe form of porphyria cutanea tarda, hepatoerythropoietic porphyria (HEP), has its onset in infancy with the accumulation of protoporphyrin in the redbloodcells. The level of the enzyme UROD is very low in red cells.
The URODgenehas been mapped to 1p34. Mutations have been identified in the UROD gene, includingDNAbase substitutions and deletions. These mutations result in reduced activity of the enzyme. Somemutationresult in porphyria cutanea tarda and others in the recessively inherited HEP. HEP is thehomozygousform of familial porphyria cutanea tarda.
Treatment is directed first at reducingironoverload by regularphlebotomy(removal of blood). Then treatment with the drug hydroxychloroquine usually induces a sustainedremission.
