Uroporphyrinogen decarboxylase deficiency

Lack of the enzyme uroporphyrinogen decarboxylase (UROD) which is the basic cause of porphyria cutanea tarda (PCT), the late skin form of porphyria. PCT is a genetic photosensitive (light-sensitive) skin disease with onset in adult life with a large amount of a substance called uroporphyrin in the urine. UROD is an enzyme required for the synthesis of heme (part of hemoglobin, the pigment in red blood cells that carries oxygen). The hallmarks of porphyria cutanea tarda (PCT) are blisters which become ulcerated in areas of the skin exposed to sunlight, especially on the face, ears and dorsum (back) of the hands. The affected areas of skin also tend to be fragile and show hyperpigmentation (excess pigment) and hypertrichosis (excess hair). PCT, the most common form of porphyria, comes in two clinical familial and a sporadic form: {{}}The familial form of PCT — is inherited as an autosomal dominant trait with males and females affected in multiple generations. The enzyme UROD is reduced in all tissues. The sporadic form of PCT — 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 PCT and may be associated with varying degrees of damage of the liver. A severe form of PCT, hepatoerythropoietic porphyria (HEP), has its onset in infancy with the accumulation of protoporphyrin in the red blood cells. The level of the enzyme UROD is very low in red cells. The UROD gene has been mapped to 1p34. Mutations have been identified in the UROD gene, including DNA base substitutions and deletions. These mutations result in reduced activity of the enzyme. Some mutation result in PCT and others in the recessively inherited HEP. HEP is the homozygous form of familial PCT. Treatment is directed first at reducing iron overload by regular phlebotomy (removal of blood). Then treatment with the drug chloroquine usually induces rapid remission that is sustained while chloroquine is continued in regular low doses.