Porphyria
What is porphyria?
Porphyria is a term that refers to a group of disorders—the porphyrias—that affect the nervous system or skin, or both. Each type of porphyria is due to the deficiency of one of the enzymes needed to make a substance in the body called heme. Enzymes are proteins that help chemical reactions happen in the body. Making heme involves a series of eight different enzymes, each acting in turn.
Heme is a red pigment composed of iron linked to a chemical called protoporphyrin. Heme has important functions in the body. The largest amounts of heme are in the blood and bone marrow in the form of hemoglobin within red blood cells. Hemoglobin gives blood its red color and carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of proteins that have many functions, including breaking down hormones, drugs, and other chemicals and generating high-energy compounds that keep liver cells alive and functioning normally.
The body makes heme mainly in the bone marrow and the liver. The process of making heme is called the heme biosynthetic pathway. Each step of the process is controlled by one of eight enzymes. If any one of the enzymes is deficient, the process is disrupted. As a result, porphyrin or its precursors—chemicals formed at earlier steps of the process—may build up in body tissues and cause illness.
What are the types of porphyria?
The table below lists each type of porphyria and the deficient enzyme responsible for the disorder. Porphyrias are often classified as acute or cutaneous. Acute types of porphyria affect the nervous system, whereas cutaneous types mainly affect the skin. Two forms of porphyria—hereditary coproporphyria and variegate porphyria—may be either acute or cutaneous, or both.
| Type of Porphyria | Deficient Enzyme |
|---|---|
| Acute Porphyrias | |
| ALAD porphyria | delta-aminolevulinic acid dehydratase |
| acute intermittent porphyria | porphobilinogen deaminase |
| hereditary coproporphyria | coproporphyrinogen oxidase |
| variegate porphyria | protoporphyrinogen oxidase |
| Cutaneous Porphyrias | |
| congenital erythropoietic porphyria | uroporphyrinogen III cosynthase |
| porphyria cutanea tarda | uroporphyrinogen decarboxylase (~50% deficiency) |
| hepatoerythropoietic porphyria | uroporphyrinogen decarboxylase (~90% deficiency) |
| hereditary coproporphyria | coproporphyrinogen oxidase |
| variegate porphyria | protoporphyrinogen oxidase |
| erythropoietic protoporphyria | ferrochelatase |
The most common type of porphyria overall is porphyria cutanea tarda. In the United States, acute intermittent porphyria is the most common acute porphyria.
What causes porphyria?
Most porphyrias are inherited disorders, meaning they are caused by abnormalities in genes passed from parents to children. Scientists have identified the genes for all eight enzymes in the heme pathway. Some forms of porphyria result from inheriting an abnormal gene from one parent. Other forms are due to inheriting two abnormal genes—one from each parent. The risk that members of an affected family will have the disease or transmit it to their children depends on the type of porphyria.
One type of porphyria—porphyria cutanea tarda—is most often an acquired disorder. It occurs when factors other than genes cause an enzyme deficiency in the liver.
Porphyria can be triggered by
- drugs such as barbiturates, tranquilizers, birth control pills, and sedatives
- chemicals
- fasting
- smoking
- drinking alcohol, especially heavy drinking
- infections
- excess iron in the body
- emotional and physical stress
- menstrual hormones
- exposure to the sun
What are the symptoms of porphyria?
People with cutaneous forms of porphyria develop blisters, itching, and swelling of their skin when it is exposed to sunlight. Symptoms of acute forms of porphyria include pain in the abdomen, chest, limbs, or back; numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. Acute attacks of porphyria can develop over hours or days and last for days or weeks.
Symptoms can vary widely in severity. Some people with gene mutations that can cause porphyria have no signs or symptoms of the disorder. These people are said to have latent porphyria.
How is porphyria diagnosed?
Doctors diagnose porphyria using blood, urine, and stool tests. Interpreting test results can be complex, and initial tests may be followed by further testing to confirm the diagnosis. Diagnosis may be delayed because the symptoms of porphyria are similar to symptoms of other disorders.
How is porphyria treated?
Each type of porphyria is treated differently. Treatment may involve avoiding triggers, receiving heme through a vein, taking medicines to relieve symptoms, or having blood drawn to reduce iron in the body. People who have severe attacks may need to be hospitalized.
Points to Remember
- Porphyria is a group of disorders—the porphyrias—that affect the nervous system or skin, or both.
- Each type of porphyria results from a deficiency of one of the enzymes needed to make heme.
- Most porphyrias are inherited disorders, but porphyria cutanea tarda is usually an acquired disorder.
- Cutaneous types of porphyria affect the skin, causing symptoms such as blistering, itching, and swelling.
- Acute types of porphyria affect the nervous system, causing symptoms such as abdominal pain, vomiting, numbness, and mental disorders.
- Each type of porphyria is treated differently.