Porphyria

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What are porphyrias?

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.

What are the types of porphyria?

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
Type of Acute Porphyria Parts of the Body Affected Where Porphyrins or Porphyrin Precursors Build Up
acute intermittent porphyria nervous system liver
variegate porphyria nervous system and skin
liver
hereditary coproporphyria nervous system and skin liver
delta-aminolevulinic acid (ALA) dehydratase deficiency porphyria nervous system liver

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
Type of Cutaneous Porphyria Parts of the Body Affected Where Porphyrins Build Up
porphyria cutanea tarda skin liver
protoporphyrias: erythropoietic protoporphyria and x-linked protoporphyria skin bone marrow
congenital erythropoietic porphyria skin bone marrow
hepatoerythropoietic porphyria skin liver

How common are porphyrias?

Porphyrias are rare diseases. Studies suggest that all types of porphyrias combined affect fewer than 200,000 people in the United States.1

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.2

The most common type of porphyria in children is a cutaneous porphyria called erythropoietic protoporphyria.3

Who is more likely to get porphyria?

Acute porphyria is more common in females than in males and often begins when people are between the ages of 15 and 45.4

Among types of cutaneous porphyria, porphyria cutanea tarda most often develops in people older than age 40, usually men.2 For other types of cutaneous porphyria, symptoms often appear in early childhood.

What are the complications of porphyrias?

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.5

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.

What are the symptoms of porphyrias?

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, 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
Woman with abdominal pain talking with a doctor.Symptoms of acute porphyria may include severe pain in the abdomen that lasts for hours to days.

Most people with acute porphyria only have one or a few attacks throughout their lives.6 Among people diagnosed with acute porphyria after one attack, about 3 to 5 percent will have four or more attacks in a year.7

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

What causes porphyrias?

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 2015–2020 Dietary Guidelines for Americans 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 use, which the 2015–2020 Dietary Guidelines for Americans defines as 15 or more drinks per week for men and 8 or more 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.

How do doctors diagnose porphyrias?

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.

How do doctors treat porphyrias?

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.4

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.8
  • 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.9 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.
Woman closing window curtainsIf you have any type of cutaneous porphyria, your doctor will recommend steps to protect your skin from sunlight.

How do doctors prevent and treat complications of porphyria?

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.

How do porphyrias affect eating, diet, and nutrition?

If you have acute porphyria, your doctor may recommend a balanced diet in which 60 to 70 percent of your calories come from carbohydrates.8 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.

Clinical Trials for Porphyria

The NIDDK conducts and supports clinical trials in many diseases and conditions, including liver diseases. The trials look to find new ways to prevent, detect, or treat disease and improve quality of life.

What are clinical trials for porphyria?

Clinical trials—and other types of clinical studies—are part of medical research and involve people like you. When you volunteer to take part in a clinical study, you help doctors and researchers learn more about disease and improve health care for people in the future.

Researchers are studying many aspects of porphyria, such as new treatments to prevent acute porphyria attacks or relieve symptoms of cutaneous porphyria. Find out if clinical studies are right for you.

What clinical studies for porphyria are looking for participants?

You can find clinical studies on porphyria at www.ClinicalTrials.gov. In addition to searching for federally funded studies, you can expand or narrow your search to include clinical studies from industry, universities, and individuals; however, the NIH does not review these studies and cannot ensure they are safe. Always talk with your health care provider before you participate in a clinical study.

How is NIDDK- and NIH-funded research advancing the understanding of porphyria?

The NIDDK and the NIH have supported many research projects to learn more about porphyria, including the Porphyrias Consortium of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences. The Porphyrias Consortium conducts research to advance our understanding of porphyrias and to improve diagnosis and treatment.

References

July 2020
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This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.

The NIDDK would like to thank:
Herbert L. Bonkovsky, M.D., Wake Forest School of Medicine