What are porphyrias?Porphyrias are rare disorders that affect mainly the skin or nervous system and may cause abdominal pain. These disorders are usually inherited, meaning they are caused by abnormalities in genes passed from parents to children. When a person has a porphyria, cells fail to change body chemicals called porphyrins and porphyrin precursors into heme, the substance that gives blood its red color. The body makes heme mainly in the bone marrow and liver. Bone marrow is the soft, spongelike tissue inside the bones; it makes stem cells that develop into one of the three types of blood cells—red blood cells, white blood cells, and platelets.
The process of making heme is called the heme biosynthetic pathway. One of eight enzymes controls each step of the process. The body has a problem making heme if any one of the enzymes is at a low level, also called a deficiency. Porphyrins and porphyrin precursors of heme then build up in the body and cause illness.
What is heme and what does it do?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 form of hemoglobin, found in red blood cells and bone marrow. Hemoglobin carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of proteins that break down hormones, medications, and other chemicals and keep liver cells functioning normally. Heme is an important part of nearly every cell in the body.
What are the types of porphyria?Each of the eight types of porphyria corresponds to low levels of a specific enzyme in the heme biosynthetic pathway. Experts often classify porphyrias as acute or cutaneous based on the symptoms a person experiences:
- Acute porphyrias affect the nervous system. They occur rapidly and last only a short time.
- Cutaneous porphyrias affect the skin.
Experts also classify porphyrias as erythropoietic or hepatic:
- In erythropoietic porphyrias, the body overproduces porphyrins, mainly in the bone marrow.
- In hepatic porphyrias, the body overproduces porphyrins and porphyrin precursors, mainly in the liver.
Table 1. Types of porphyria
|Type of Porphyria||Deficient Enzyme||Main Location of Porphyrin Buildup|
|delta-aminolevulinate-dehydratase deficiency porphyria||delta-aminolevulinic acid dehydratase||liver|
|acute intermittent porphyria||porphobilinogen deaminase||liver|
|hereditary coproporphyria||coproporphyrinogen oxidase||liver|
|variegate porphyria||protoporphyrinogen oxidase||liver|
|congenital erythropoietic porphyria||uroporphyrinogen III cosynthase||bone marrow|
|porphyria cutanea tarda||uroporphyrinogen decarboxylase (~75% deficiency)||liver|
|hepatoerythropoietic porphyria||uroporphyrinogen decarboxylase (~90% deficiency)||bone marrow|
|erythropoietic protoporphyria*||ferrochelatase (~75% deficiency)||bone marrow|
How common is porphyria?The exact rates of porphyria are unknown and vary around the world. For example, porphyria cutanea tarda is most common in the United States, and variegate porphyria is most common in South America.1
What causes porphyria?Most porphyrias are inherited disorders. Scientists have identified genes for all eight enzymes in the heme biosynthetic pathway. Most porphyrias result from inheriting an abnormal gene, also called a gene mutation, from one parent. Some porphyrias, such as congenital erythropoietic porphyria, hepatoerythropoietic porphyria, and erythropoietic protoporphyria, occur when a person inherits two abnormal genes, one from each parent. The likeliness of a person passing the abnormal gene or genes to the next generation depends on the type of porphyria.
Porphyria cutanea tarda is usually an acquired disorder, meaning factors other than genes cause the enzyme deficiency. This type of porphyria can be triggered by
- too much iron
- use of alcohol or estrogen
- chronic hepatitis C—a long-lasting liver disease that causes inflammation, or swelling, of the liver
- HIV—the virus that causes AIDS
- abnormal genes associated with hemochromatosis—the most common form of iron overload disease, which causes the body to absorb too much iron
- use of alcohol
- use of certain medications or hormones
- exposure to sunlight
- dieting and fasting
What are the symptoms of porphyria?Some people with porphyria-causing gene mutations have latent porphyria, meaning they have no symptoms of the disorder. Symptoms of cutaneous porphyrias include
- oversensitivity to sunlight
- blisters on exposed areas of the skin
- itching and swelling on exposed areas of the skin
- pain in the abdomen—the area between the chest and hips
- pain in the chest, limbs, or back
- nausea and vomiting
- constipation—a condition in which an adult has fewer than three bowel movements a week or a child has fewer than two bowel movements a week, depending on the person
- urinary retention—the inability to empty the bladder completely
- seizures and muscle weakness
How is porphyria diagnosed?A health care provider diagnoses porphyria with blood, urine, and stool tests. These tests take place at a health care provider’s office or a commercial facility. A blood test involves drawing blood and sending the sample to a lab for analysis. For urine and stool tests, the patient collects a sample of urine or stool in a special container. A health care provider tests the samples in the office or sends them to a lab for analysis. High levels of porphyrins or porphyrin precursors in blood, urine, or stool indicate porphyria. A health care provider may also recommend DNA testing of a blood sample to look for known gene mutations that cause porphyrias.
How is porphyria treated?Treatment for porphyria depends on the type of porphyria the person has and the severity of the symptoms.
Acute PorphyriasA health care provider treats acute porphyrias with heme or glucose loading to decrease the liver’s production of porphyrins and porphyrin precursors. A patient receives heme intravenously once a day for 4 days. Glucose loading involves giving a patient a glucose solution by mouth or intravenously. Heme is usually more effective and is the treatment of choice unless symptoms are mild. In rare instances, if symptoms are severe, a health care provider will recommend liver transplantation to treat acute porphyria. In liver transplantation, a surgeon removes a diseased or an injured liver and replaces it with a healthy, whole liver or a segment of a liver from another person, called a donor. A patient has liver transplantation surgery in a hospital under general anesthesia. Liver transplantation can cure liver failure. More information is provided in the NIDDK health topic, Liver Transplantation.
Cutaneous PorphyriasThe most important step a person can take to treat a cutaneous porphyria is to avoid sunlight as much as possible. Other cutaneous porphyrias are treated as follows:
- Porphyria cutanea tarda. A health care provider treats porphyria cutanea tarda by removing factors that tend to activate the disease and by performing repeated therapeutic phlebotomies to reduce iron in the liver. Therapeutic phlebotomy is the removal of about a pint of blood from a vein in the arm. A technician performs the procedure at a blood donation center, such as a hospital, clinic, or bloodmobile. A patient does not require anesthesia. Another treatment approach is low-dose hydroxychloroquine tablets to reduce porphyrins in the liver.
- Erythropoietic protoporphyria. People with erythropoietic protoporphyria may be given beta-carotene or cysteine to improve sunlight tolerance, though these medications do not lower porphyrin levels. Experts recommend hepatitis A and B vaccines and avoiding alcohol to prevent protoporphyric liver failure. A health care provider may use liver transplantation or a combination of medications to treat people who develop liver failure. Unfortunately, liver transplantation does not correct the primary defect, which is the continuous overproduction of protoporphyria by bone marrow. Successful bone marrow transplantations may successfully cure erythropoietic protoporphyria. A health care provider only considers bone marrow transplantation if the disease is severe and leading to secondary liver disease.
- Congenital erythropoietic porphyria and hepatoerythropoietic porphyria. People with congenital erythropoietic porphyria or hepatoerythropoietic porphyria may need surgery to remove the spleen or blood transfusions to treat anemia. A surgeon removes the spleen in a hospital, and a patient receives general anesthesia. With a blood transfusion, a patient receives blood through an intravenous (IV) line inserted into a vein. A technician performs the procedure at a blood donation center, and a patient does not need anesthesia.