Porphyrias are a group of genetic disorders caused by problems with how your body makes a substance called heme. Heme is found throughout the body, especially in your blood and bone marrow, where it carries oxygen.

There are two main types of porphyrias. One affects the skin and the other affects the nervous system. People with the skin type develop blisters, itching, and swelling of their skin when it is exposed to sunlight. The nervous system type is called acute porphyria. Symptoms 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 come and go.

Certain triggers can cause an attack, including some medicines, smoking, drinking alcohol, infections, stress, and sun exposure. Attacks develop over hours or days. They can last for days or weeks.

Porphyria can be hard to diagnose. It requires blood, urine, and stool tests. 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.

Porphyrias are rare disorders that mainly affect the skin or nervous system. These disorders are usually inherited, meaning they are caused by gene mutations passed from parents to children.

If you have porphyria, cells fail to change chemicals in your body—called porphyrins and porphyrin precursors—into heme, the substance that gives blood its red color. When these chemicals build up in your body, they cause illness. Depending on the type of porphyria you have, porphyrins or porphyrin precursors may build up in the liver or the bone marrow. Bone marrow is the spongy tissue inside most of your bones.

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.

Porphyrias are rare diseases. Studies suggest that all types of porphyrias combined affect fewer than 200,000 people in the United States.

The most common type of acute porphyria is acute intermittent porphyria.

The most common type of cutaneous porphyria—and the most common type of porphyria overall—is porphyria cutanea tarda, which affects about 5 to 10 out of every 100,000 people.

The most common type of porphyria in children is a cutaneous porphyria called erythropoietic protoporphyria.

The porphyrias are a group of different diseases, each caused by a specific abnormality in the heme production process.

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.

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 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

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:

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.

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.

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.

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.

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.

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:

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.

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.

Experts often divide porphyrias into two groups—acute porphyrias and cutaneous porphyrias—based on whether they primarily affect the nervous system or the skin.

Acute porphyrias

Four types of acute porphyrias affect the nervous system. Two of those types can also affect the skin. Symptoms for acute porphyrias develop over hours or days and last for days or weeks.

Table 1. Types of acute porphyria

Cutaneous porphyrias

Four types of cutaneous porphyrias affect only the skin and cause chronic, or long lasting, symptoms. People with cutaneous porphyria may develop skin symptoms—such as blistering or pain—after their skin is exposed to sunlight.

Table 2. Types of cuteaneous porphyria

Acute intermittent porphyria (AIP) is one of the liver (hepatic) porphyrias. AIP is caused by low levels of porphobilinogen deaminase (PBGD), an enzyme also often called hydroxymethylbilane synthase. The low levels of PBGD are generally not sufficient to cause symptoms; however, activating factors such as hormones, drugs, and dietary changes may trigger symptoms. Although most individuals with AIP never develop symptoms, symptomatic individuals typically present with abdominal pain with nausea. Treatment is dependent on the symptoms.

Hereditary coproporphyria (HCP)is a rare inherited form of liver (hepatic) porphyria, characterized by neurological symptoms in the form of episodes (acute attacks) of stomach pain, nausea, vomiting, weakness, numbness, and pain in the hands and feet (neuropathy). The porphyrias are a group of blood conditions caused by a lack of an enzyme in the body that makes heme, an important molecule that carries oxygen throughout the body and is vital for all of the body’s organs.

Symptoms usually begin around 20-30 years of age, but have been reported at younger ages. Signs and symptoms present during the attacks may include body pain, nausea and vomiting, increased heart rate (tachycardia), and high blood pressure. Less common symptoms include seizures, skin lesions, and paralysis of the arms and legs, body trunk, and respiratory muscles. Most individuals with HCP do not have any signs or symptoms between attacks.

HCP is caused by mutations in the CPOX gene and is inherited in an autosomal dominant manner. Diagnosis is based on the symptoms and specific blood, urine and stool testing. Treatment is based on preventing the symptoms. An acute attack requires hospitalization, medications, and treatment with heme therapy.

Acute porphyria is more common in females than in males and often begins when people are between the ages of 15 and 45.

Among types of cutaneous porphyria, porphyria cutanea tarda most often develops in people older than age 40, usually men. For other types of cutaneous porphyria, symptoms often appear in early childhood.

Most types of porphyrias are caused by gene mutations. Some types of porphyrias result from inheriting a gene mutation from one parent, while other types result from inheriting two gene mutations, one from each parent.

Many people with gene mutations for acute porphyrias never develop the disease. In people who have these gene mutations, factors that increase the chance of developing acute porphyria attacks or make attacks worse include

• female sex hormones, especially progesterone
• some medicines, including hormonal types of birth control and certain types of antibiotics, anesthetics, and anticonvulsants—medicines designed to treat seizures
• lowered intake of carbohydrates, due to fasting, dieting, illness, or bariatric surgery
• drinking alcohol, especially binge drinking, which the National Institute on Alcohol Abuse and Alcoholism defines as having four or more drinks within about 2 hours for women and having five or more drinks within about 2 hours for men
• smoking

The most common type of porphyria, porphyria cutanea tarda, is most often acquired, meaning that factors other than inherited genes may cause this condition. These factors may include

• a buildup of iron in the body, which may be caused by gene mutations that can lead to hemochromatosis
• heavy alcohol drinking, which the National Institute on Alcohol Abuse and Alcoholism defines as more than 14 drinks per week for men and more than 7 drinks per week for women
• smoking
• viral infections, such as hepatitis C and HIV infections
• taking estrogen, which may be found in medicines such as birth control pills and hormonal replacement therapy

In some cases, an inherited gene mutation plays a role in causing porphyria cutanea tarda, along with one or more of the factors listed above.

Some types of porphyria are inherited in an autosomal dominant pattern, which means one copy of the gene in each cell is mutated. This single mutation is sufficient to reduce the activity of an enzyme needed for heme production, which increases the risk of developing signs and symptoms of porphyria. Autosomal dominant porphyrias include acute intermittent porphyria, most cases of erythropoietic protoporphyria, hereditary coproporphyria, and variegate porphyria. Although the gene mutations associated with some cases of porphyria cutanea tarda also have an autosomal dominant inheritance pattern, most people with this form of porphyria do not have an inherited gene mutation.

Other porphyrias are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. Porphyrias with an autosomal recessive pattern of inheritance include ALAD deficiency porphyria, congenital erythropoietic porphyria, and some cases of erythropoietic protoporphyria.

When erythropoietic protoporphyria is caused by mutations in the ALAS2 gene, it has an X-linked dominant pattern of inheritance. The ALAS2 gene is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may be sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. Males may experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Mutations in the UROD gene are related to both porphyria cutanea tarda and hepatoerythropoietic porphyria. Individuals who inherit one altered copy of the UROD gene are at increased risk for porphyria cutanea tarda. (Multiple genetic and nongenetic factors contribute to this condition.) People who inherit two altered copies of the UROD gene in each cell develop hepatoerythropoietic porphyria.

Acute porphyrias

Symptoms of acute porphyria can be mild or severe, lasting days or weeks. Times when symptoms occur are called attacks. Without early treatment, symptoms of an attack may become more severe and even life-threatening. Symptoms may include

• pain in the abdomen, back, or arms and legs
• digestive symptoms, such as constipation, nausea, and vomiting
• mental changes, such as anxiety NIH external link, confusion, hallucinations, and seizures
• problems with nerves that control movement, which may cause muscle weakness, paralysis, and breathing problems
• urinary symptoms, such as dark or reddish-brown urine, urinary retention, or incontinence
• skin blisters when skin is exposed to sunlight, for people with variegate porphyria or hereditary coproporphyria

Most people with acute porphyria only have one or a few attacks throughout their lives. Among people diagnosed with acute porphyria after one attack, about 3 to 5 percent will have four or more attacks in a year.

Factors that may increase the chance of getting acute porphyria attacks or make attacks worse include female sex hormones, especially progesterone; certain medicines; a lowered intake of carbohydrates; drinking alcohol; and smoking.

Cutaneous porphyrias

In people with porphyria cutanea tarda, congenital erythropoietic porphyria, or hepatoerythropoietic porphyria, areas of skin exposed to sunlight may develop symptoms such as

• blisters
• fragile skin that is easily wounded and slow to heal
• infection of blisters or wounds
• scarring or changes in skin color

Protoporphyrias—erythropoietic protoporphyria and x-linked protoporphyria—typically do not cause blisters. Instead, skin exposed to sunlight may develop symptoms such as

• pain, burning, stinging, or tingling
• redness
• swelling

Your doctor will ask about your medical history and symptoms and perform a physical exam. If a doctor suspects you may have porphyria, he or she will order tests to diagnose the disease.

Tests for porphyria

Tests for porphyria measure the amounts of porphyrins and porphyrin precursors in your blood, urine, or stool and are used to detect porphyria and to monitor the disease. Additional testing may be needed to determine what type of porphyria you have.

Genetic tests

Genetic tests check for the gene mutations that cause porphyrias. The test may help confirm the diagnosis and determine which specific gene mutation you have.

If you have a mutation, your doctor may recommend testing for the same mutation in your family members. If you or family members are considering genetic testing, you may want to consider genetic counseling. Genetic counseling can help you and your family understand how test results may affect your lives.

Treatment for porphyria will depend on what type of porphyria you have and how severe your symptoms are.

Acute porphyrias

Doctors most often treat acute porphyria attacks in a hospital. Treatment may include medicines that typically relieve symptoms in 3 or 4 days.

To prevent future attacks, your doctor may recommend

• avoiding medicines that are unsafe for people who have porphyria. Talk with your doctor before you take any over-the-counter or prescription medicines, dietary supplements, or complementary or alternative medicines, such as herbal or botanical medicines.
• eating a balanced diet and avoiding fasting or extreme diets.
• avoiding smoking.
• avoiding heavy alcohol use. Experts recommend no more than one drink per day for women and no more than two drinks per day for men.
• medicines to help reduce the number of future attacks. Some medicines prescribed to reduce the number of attacks can be costly. Talk with your doctor about your health insurance coverage.

In rare cases, doctors may recommend a liver transplant. Doctors only recommend a liver transplant if a person has repeated, severe attacks and other treatments don’t work.

If you have a type of acute porphyria that causes skin symptoms, treatment may include protecting your skin from sunlight.

Cutaneous porphyrias

If you have any type of cutaneous porphyria, your doctor will recommend steps to protect your skin from sunlight. Doctors may prescribe different treatments for different types of cutaneous porphyria.

• Doctors typically treat porphyria cutanea tarda either with phlebotomy, which typically involves drawing about a pint of blood every 2 weeks until iron levels in the body have been reduced, or with medicines. During treatment, doctors will order regular blood tests to check your iron and porphyrin levels.With treatment, most people go into remission, meaning they don’t have symptoms after their skin is exposed to sunlight and their porphyrin levels return to normal. To help people go into and stay in remission, doctors also recommend avoiding or eliminating factors that can cause porphyria cutanea tarda.
• For erythropoietic protoporphyria, doctors may prescribe medicine that allows people with the disease to spend more time in sunlight without pain.
• For some children with congenital erythropoietic porphyria who have severe symptoms, doctors may recommend a bone marrow transplant, using healthy stem cells from a donor.

Different types of porphyrias may lead to different complications.

Liver problems

Several types of porphyrias can cause liver problems. Acute porphyria increases the chance of developing liver cancer. Porphyria cutanea tarda can damage the liver and increase the chance of developing cirrhosis and liver cancer. Some people with protoporphyria also develop liver damage and cirrhosis, and up to 5 percent of people with protoporphyria develop liver failure.

In people with protoporphyria, bile carries extra porphyrins from the liver to the gallbladder, which may lead to gallstones that are made of porphyrins.

Anemia

Two types of cutaneous porphyria, congenital erythropoietic porphyria and, less commonly, hepatoerythropoietic porphyria, may cause severe anemia. These diseases may also cause the spleen to become enlarged, which can make anemia worse.

High blood pressure and kidney problems

People with acute porphyria have an increased chance of developing high blood pressure and chronic kidney disease, which can lead to kidney failure.

Depending on the type of porphyria you have, your doctor may recommend steps to prevent or treat complications.

Liver problems

For porphyria cutanea tarda, treating the disease can help prevent liver problems.

Porphyria cutanea tarda and acute porphyria can increase the risk of developing liver cancer. Depending on your risk, your doctor may recommend blood tests and an ultrasound or another type of imaging test to check for liver cancer. Finding cancer at an early stage improves the chance of curing the cancer.

In people with protoporphyria, doctors may recommend protecting the liver by avoiding alcohol and getting hepatitis A and hepatitis B vaccines. If protoporphyria leads to liver failure, you may need a liver transplant. In some cases, doctors may also recommend a bone marrow transplant, which can cure protoporphyria and keep the disease from damaging the new liver.

If protoporphyria leads to gallstones, treatment typically involves surgery to remove the gallbladder.

Anemia

People with congenital erythropoietic porphyria or hepatoerythropoietic porphyria who develop severe anemia may require treatment with blood transfusions. In some cases, doctors may also recommend surgery to remove an enlarged spleen, which can help treat anemia.

High blood pressure and kidney problems

If you have acute porphyria, your doctor may check for complications such as high blood pressure and chronic kidney disease, which may lead to kidney failure. Your doctor may prescribe medicines to lower blood pressure and recommend steps to manage chronic kidney disease or treatments for kidney failure.

If you have acute porphyria, your doctor may recommend a balanced diet in which 60 to 70 percent of your calories come from carbohydrates. Lowering your intake of carbohydrates and calories, even for a short time, can cause an acute porphyria attack. Talk with your doctor or a dietitian before changing your diet to try to lose weight. They can help you plan a safe diet to lose weight gradually.

People with cutaneous porphyrias who need to avoid sunlight may have lower levels of vitamin D. Doctors may recommend vitamin D supplements to treat low vitamin D levels.