Information on the following diseases can be found in the Related Disorders section of this report:

• Porphyrias
• ALA-D Porphyria
• Acute Intermittent Porphyria
• Congenital Erythropoietic Porphyria (CEP)
• Hereditary Coproporphyria (HCP)
• Variegate Porphyria (VP)
• Erythropoietic Protoporphyria (EPP)

The symptoms of porphyria cutanea tarda are usually confined to the skin. Blistering after exposure to sunlight and/or minor trauma may occur on the hands, face and other sun-exposed areas. Skin fragility, increased hair growth, and darkening and thickening of the skin may also occur. Urine may be reddish in color due to the presence of excess porphyrins and related substances, and the urine may darken after being exposed to the light.

Neurological and abdominal symptoms are not characteristic of PCT. Liver function abnormalities are common but are often mild. PCT has been associated with the development of liver cancer in individuals who are also heavy alcohol drinkers and have developed cirrhosis.

Porphyria is a group of at least seven metabolic disorders that arise as a result of a malfunction in one of the eight steps in the body’s synthesis of a complex molecule called heme. Heme is essential for the transport of oxygen to cells in the body. If any step in the synthesis of heme is blocked, an intermediate chemical accumulates in the cell, resulting in oxygen depletion. Those intermediate chemicals, known as porphyrins or porphyrin precursors, are the substances of which heme is composed.

Each type of porphyria represents a deficiency of a specific enzyme needed for the synthesis of heme. PCT results from a deficiency of the enzyme uroporphyrinogen decarboxylase (URO-D) in the liver that can be caused by an inherited gene mutation or acquired factors. Approximately 20% of affected individuals have the inherited type of PCT and 80% have the acquired type.

The inherited form of PCT is also called familial PCT and follows autosomal dominant inheritance. Familial PCT is caused by an abnormality in the UROD gene that controls the production of the URO-D enzyme.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

PCT becomes active and causes symptoms when triggered by an environmental factor that affects liver cells (hepatocytes). These environmental factors include alcohol, estrogens, hepatitis C, human immunodeficiency viruses (HIV) and excess iron in tissues due to hemochromatosis or other conditions. It is usually necessary for an environmental trigger to be present to cause symptoms of either the acquired or inherited type of PCT.

PCT is the most common type of porphyria and is more common in males than females. It usually occurs in adulthood but sometimes occurs in childhood. The estimated prevalence of both inherited and acquired PCT is 1 in 25,000 people.

The porphyrias are a group of related disorders. For more information on each of the following types of the disease, choose "porphyria" as your search term in the Rare Disease Database.

Acute intermittent porphyria is an autosomal dominant porphyria associated with abdominal, arm and leg pain, generalized weakness, vomiting, confusion, constipation, tachycardia, fluctuating blood pressure, urinary retention, psychosis, hallucinations, and seizures. Urine may exhibit a purple-red color. Unlike other forms of porphyria, sun sensitivity is not present in this type. The muscle weakness may progress to respiratory paralysis, necessitating artificial respiration.

Variegate porphyria is an autosomal dominant porphyria characterized by sensitivity to sunlight leading to abrasions, blisters, and erosions of the skin which are commonly seen during the second and third decade. These lesions tend to heal slowly and often leave pigmented or slightly depressed scars. Some affected individuals also have episodes similar to those of acute intermittent porphyria.

Hereditary coproporphyria is an autosomal dominant porphyria that is similar to acute intermittent porphyria but can also include sensitivity to sunlight.

Protoporphyria is an autosomal dominant porphyria associated with mild to severe light sensitivity and burning on exposure to the sunlight. Symptoms usually begin in childhood. They are more severe in the summer and can recur throughout life. Rarely, significant liver damage can also occur.

Congenital erythropoietic porphyria is a rare autosomal recessive type of porphyria that is usually diagnosed shortly after birth and characterized by dark urine and sunlight sensitivity causing blistering and skin fragility. Later, brownish, fluorescent teeth, increased hair growth, and pronounced scarring may occur. The effects of sun damage and infection can lead to the loss of fingers and toes and cartilage from ears or nose in some affected individuals.

ALA-D porphyria is a rare autosomal recessive type of porphyria that is very similar to acute intermittent porphyria. The disease usually manifests after puberty, and is more common in women

Hepatoerythropoietic porphyria is a rare autosomal recessive type of porphyria characterized by skin blistering that usually begins in infancy.

Diagnosis
The preferred screening test for PCT is the measurement of porphyrins in blood plasma. This can differentiate PCT from variegate porphyria. The patterns of porphyrins in urine (predominately uroporphyrin and 7-carboxylate porphyrin) and feces (predominately isocoproporphyrin) help to confirm the diagnosis. Familial PCT can be diagnosed by the presence of a reduced amount of the UROD enzyme in red blood cells. Molecular genetic testing is available for familial PCT if the diagnosis has been confirmed in the patient or a family member by urinary porphyrin analysis and/or enzyme assay of UROD.

Treatment
PCT is the most treatable type of porphyria. The standard treatment for PCT is repeated letting of blood (phlebotomy) to reduce iron in the liver. Phlebotomies are stopped when the measurement of ferritin in blood serum falls to approximately 20 ng/ml. Low doses of chloroquine and hydroxychloroquine can also be used to reduce serum ferritin.

Individuals with PCT should avoid the environmental triggers for the disease such as alcohol, estrogens and iron supplements.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Anderson KE. Porphyria Cutanea Tarda. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003: 493-4.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 176100; Lat Update: 3/17/04.

Poh-Fitzpatrick MB. Porphyria Cutanea Tarda. eMedicine. Last Updated: 6/5/03.

Anderson KE, Sassa S, Bishop D, et al. Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. In: Scriver CR, Beaudet Al, Sly WS, et al., eds. The metabolic and molecular basis of inherited disease, 8th ed. New York: McGraw-Hill, 2000:2991-3062.

Egger NE, Goeger DE, Payne DA, et al. Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C and inherited uroporphryrinogen decarboxylase deficiency. Dig Dis Sci 2002;47:419-426.