Porphyria cutanea tarda (PCT) is a rare disorder characterized by painful, blistering skin lesions that develop on sun-exposed skin (photosensitivity). Affected skin is fragile and may peel or blister after minor trauma. Liver abnormalities may also occur. PCT is caused by deficient levels of an enzyme known as uroporphyrinogen decarboxylase (UROD). In approximately 75% to 80% of cases this deficiency is acquired (PCT type 1 or sporadic PCT); in the remaining cases, individuals have a genetic predisposition to developing the disorder, specifically a mutation in the UROD gene (PCT type 2 or familial PCT). Most individuals with this genetic mutation do not develop PCT; the mutation is a predisposing factor and additional factors are required for the development of the disorder in these individuals. These factors are called susceptibility factors and are required for the development of both sporadic and familial PCT. Generally, PCT develops in mid to late adulthood. In extremely rare cases, individuals have mutations in both UROD genes. This autosomal recessive form of familial PCT is known as hepatoerythropoietic porphyria (HEP). HEP occurs in childhood and is usually more severe than PCT types 1 or 2. NORD has a separate report on HEP.
PCT belongs to a group of disorders known as the porphyrias. This group of at least seven disorders is characterized by abnormally high levels of porphyrins and porphyrin precursors due to deficiency of certain enzymes essential to the creation (synthesis) of heme, a part of hemoglobin and other hemoproteins. There are eight enzymes in the pathway for making heme and at least seven major forms of porphyria. The symptoms associated with the various forms of porphyria differ. It is important to note that people who have one type of porphyria do not develop any of the other types. Porphyrias are generally classified into two groups: the “hepatic” and “erythropoietic” types. Porphyrins and porphyrin precursors and related substances originate in excess amounts predominantly from the liver in the hepatic types and mostly from the bone marrow in the erythropoietic types. Porphyrias with skin manifestations are sometimes referred to as “cutaneous porphyrias.” The term “acute porphyria” is used to describe porphyrias that can be associated with sudden attacks of pain and other neurological symptoms. Most forms of porphyria are genetic inborn errors of metabolism. PCT is an acquired liver disease, in which some individuals have a genetic predisposition to developing the disorder.