Porphyria

What is porphyria?
The porphyrias are a group of different diseases, each caused by a specific abnormality in the heme production process. Heme is a chemical compound that contains iron and gives blood its red color. The essential functions of heme depend on its ability to bind oxygen. Heme is incorporated into hemoglobin, a protein that enables red blood cells to carry oxygen from the lungs to all parts of the body. Heme also plays a role in the liver where it assists in breaking down chemicals (including some drugs and hormones) so that they are easily removed from the body.

Heme is produced in the bone marrow and liver through a complex process controlled by eight different enzymes. As this production process of heme progresses, several different intermediate compounds (heme precursors) are created and modified. If one of the essential enzymes in heme production is deficient, certain precursors may accumulate in tissues (especially in the bone marrow or liver), appear in excess in the blood, and get excreted in the urine or stool. The specific precursors that accumulate depend on which enzyme is deficient. Porphyria results in a deficiency or inactivity of a specific enzyme in the heme production process, with resulting accumulation of heme precursors.

What are the signs and symptoms of porphyria?
The signs and symptoms of porphyria vary among types. Some types of porphyria (called cutaneous porphyria) cause the skin to become overly sensitive to sunlight. Areas of the skin exposed to the sun develop redness, blistering and often scarring.

The symptoms of other types of porphyria (called acute porphyrias) affect the nervous system. These symptoms include chest and abdominal pain, emotional and mental disorders, seizures and muscle weakness. These symptoms often appear quickly and last from days to weeks. Some porphyrias have a combination of acute symptoms and symptoms that affect the skin.

Environmental factors can trigger the signs and symptoms of porphyria. These include:
• Alcohol
• Smoking
• Certain drugs, hormones
• Exposure to sunlight
• Stress
• Dieting and fasting

How is porphyria diagnosed?
Porphyria is diagnosed through blood, urine, and stool tests, especially at or near the time of symptoms. Diagnosis may be difficult because the range of symptoms is common to many disorders and interpretation of the tests may be complex. A large number of tests are available, however, but results among laboratories are not always reliable.

How is porphyria treated?
Each form of porphyria is treated differently. Treatment may involve treating with heme, giving medicines to relieve the symptoms, or drawing blood. People who have severe attacks may need to be hospitalized.

What do we know about porphyria and heredity?
Most of the porphyrias are inherited conditions. The genes for all the enzymes in the heme pathway have been identified. Some forms of porphyria result from inheriting one altered gene from one parent (autosomal dominant). Other forms result from inheriting two altered genes, one from each parent (autosomal recessive). Each type of porphyria carries a different risk that individuals in an affected family will have the disease or transmit it to their children.

Porphyria cutanea tarda (PCT) is a type of porphyria that is most often not inherited. Eighty percent of individuals with PCT have an acquired disease that becomes active when factors such as iron, alcohol, hepatitis C virus (HCV), HIV, estrogens (such as those used in oral contraceptives and prostate cancer treatment), and possibly smoking, combine to cause an enzyme deficiency in the liver. Hemochromatosis, an iron overload disorder, can also predispose individuals to PCT. Twenty percent of individuals with PCT have an inherited form of the disease. Many individuals with the inherited form of PCT never develop symptoms.

If you or someone you know has porphyria, we recommend that you contact a genetics clinic to discuss this information with a genetics professional. To find a genetics clinic near you, contact your primary doctor for a referral.

What triggers a porphyria attack?
Porphyria can be triggered by drugs (barbiturates, tranquilizers, birth control pills, sedatives), chemicals, fasting, smoking, drinking alcohol, infections, emotional and physical stress, menstrual hormones, and exposure to the sun. Attacks of porphyria can develop over hours or days and last for days or weeks.

How is porphyria classified?
The porphyrias have several different classification systems. The most accurate classification is by the specific enzyme deficiency. Another classification system distinguishes porphyrias that cause neurologic symptoms (acute porphyrias) from those that cause photosensitivity (cutaneous porphyrias). A third classification system is based on whether the excess precursors originate primarily in the liver (hepatic porphyrias) or primarily in the bone marrow (erythropoietic porphyrias). Some porphyrias are classified as more than one of these categories.

What are the cutaneous porphyrias?
The cutaneous porphyrias affect the skin. People with cutaneous porphyria develop blisters, itching, and swelling of their skin when it is exposed to sunlight. The cutaneous porphyrias include the following types:

Congenital erythropoietic porphyria. Also called congenital porphyria. This is a rare disorder that mainly affects the skin. It results from low levels of the enzyme responsible for the fourth step in heme production. It is inherited in an autosomal recessive pattern.

Erythropoietic protoporphyria. An uncommon disorder that mainly affects the skin. It results from reduced levels of the enzyme responsible for the eighth and final step in heme production. The inheritance of this condition is not fully understood. Most cases are probably inherited in an autosomal dominant pattern, however, it shows autosomal recessive inheritance in a small number of families.

Hepatoerythropoietic porphyria. A rare disorder that mainly affects the skin. It results from very low levels of the enzyme responsible for the fifth step in heme production. It is inherited in an autosomal recessive pattern.

Hereditary coproporphyria. A rare disorder that can have symptoms of acute porphyria and symptoms that affect the skin. It results from low levels of the enzyme responsible for the sixth step in heme production. It is inherited in an autosomal dominant pattern.

Porphyria cutanea tarda.The most common type of porphyria. It occurs in an estimated 1 in 25,000 people, including both inherited and sporadic (noninherited) cases. An estimated 80 percent of porphyria cutanea tarda cases are sporadic. It results from low levels of the enzyme responsible for the fifth step in heme production. When this condition is inherited, it occurs in an autosomal dominant pattern.

Variegate porphyria. A disorder that can have symptoms of acute porphyria and symptoms that affect the skin. It results from low levels of the enzyme responsible for the seventh step in heme production. It is inherited in an autosomal dominant pattern.

What are the acute porphyrias?
The acute porphyrias affect the nervous system. Symptoms of acute porphyria include pain in the chest, abdomen, limbs, or back; muscle numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms appear intermittently. The acute porphyrias include the following types:

Acute intermittent porphyria. This is probably the most common porphyria with acute (severe but usually not long-lasting) symptoms. It results from low levels of the enzyme responsible for the third step in heme production. It is inherited in an autosomal dominant pattern.

ALAD deficiency porphyria. A very rare disorder that results from low levels of the enzyme responsible for the second step in heme production. It is inherited in an autosomal recessive pattern.

Additional resources
American Porphyria Foundation
49 Woodway, Suite 780
Houston, TX 77056
866-APF-3635
porphyriafoundation.org/

British Porphyria Association
136 Devonshire Rd
Durham City
DH1 2BL
01474369231
porphyria.org.uk/

Canadian Porphyria Foundation, Inc.
487 Walker Avenue, Box 1206
Neepawa, MB R0J 1H0
866-476-2801

Iron Disorders Institute
PO Box 675
Taylors, SC, 29678
888-565-IRON (4766)
https://www.irondisorders.org/

American Liver Foundation (ALF)
75 Maiden Lane, Suite 603
New York, NY 10038-4810
1-800-GO-LIVER (465-4837),
1-888-4HEP-USA (443-7872),
or 212-668-1000
https://www.liverfoundation.org

This information was developed by the National Human Genome Research Institute.

National Human Genome Research Institute. Learning About Porphyria. Available at: https://www.genome.gov/19016728. Last accessed December 31, 2017.

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