Frequently Asked Questions About the Porphyrias

Please visit the United Porphyrias Association website to learn about what the porphyrias are, how they are caused, and get detailed information on each type of porphyria.

Please see the United Porphyrias Association website for information on how to diagnose the different types of porphyria.

There are many laboratory tests available for the porphyrias, and the correct tests to order depend on the type of porphyria the doctor suspects. It is best to have the testing performed by a laboratory that has expertise in the clinical aspects of porphyria and can provide a valid interpretation of the test results. If testing has been performed in laboratories other than porphyria laboratories, consultation with a porphyria expert is advised before a final diagnosis is made.

The table below summarizes the tests to be done for each type of porphyria.

Genetic Testing

DNA testing is an accurate and reliable method for determining if a person has a specific porphyria in addition to biochemical testing. If a change (called a pathogenic variant) in the DNA sequence is found in a specific porphyria-causing gene, the diagnosis of that porphyria is confirmed. DNA testing can be performed whether the patient is symptomatic or not. Once a change has been identified, DNA analysis can then be performed on other family members to determine if they have inherited that porphyria, thus allowing identification of individuals who can be counseled about appropriate management in order to avoid or minimize disease complications.

A VUS is when a change in a gene is detected, but the impact that change has on the gene’s function is unknown. Therefore, it is not certain whether that change is causing porphyria or not. More information on VUS’s can be found here.

Enzyme testing is a blood test to measure the activity level of a particular porphyria-specific enzyme, which is responsible for breaking down compounds in the body. This type of testing is not commonly done, and is not considered diagnostic for the porphyrias.

There are porphyria experts in the US and outside the US, including the porphyria centers in this Physicians Consortium. Information about other experts can be obtained by contacting the United Porphyrias Association. If a porphyria is suspected, any physician can order the appropriate tests. Since interpretation of these results may be difficult, it is best for the physician or healthcare professional to consult with a porphyria expert for an accurate interpretation of the results and, if necessary, advice about additional testing, treatment, or prevention and precautionary measures. If you have been diagnosed with a porphyria you may need to see different specialists to ensure all aspects of the condition are being managed properly.

If your genetic (DNA) testing results were negative and your doctor still suspects a porphyria, they should do biochemical testing.

Because all porphyrias are rare, it is very unlikely that more than one type of porphyria will occur in the same family, or that a person with one type of porphyria will have an additional type. However, people with more than one type of porphyria have been reported.

The liver is affected differently for each type of porphyria. Please refer to the disorder definitions page about your type of porphyria for more information on how the liver is involved. Although the different types of porphyria affect the liver differently, liver function tests should be performed routinely (usually annually).

These situations needs to be dealt with on an individual basis. Whether further testing is recommended depends on how the person was initially diagnosed and how the porphyria expert made the decision that porphyria is not the diagnosis. The results of biochemical testing are sometimes interpreted incorrectly by a physician who is not an expert in porphyria. Review of the biochemical testing results by a porphyria expert may determine that the results are not diagnostic. The results of DNA analysis may also contribute to the porphyria expert saying that it is unlikely that the patient has porphyria. DNA analysis is not perfect. The person may have a change in a part of the porphyria gene that is not analyzed by routine testing or the person has a change in a porphyria gene that was not analyzed. In the event that a diagnosis of porphyria is still suspected, then it is recommended that additional biochemical testing be done. Additionally, further testing may include DNA analysis for other porphyria genes (if only one or two were tested).

Yes, we are conducting research about the porphyrias. For additional information about our studies and how to volunteer to participate, please see the United Porphyrias Association website.

None of the porphyrias are contagious. However, for one type of porphyria, porphyria cutanea yarda (PCT), one of the major risk factors for development it is infection with the hepatitis C virus (HCV). A lesser risk factor for PCT is infection with the human immunodeficiency virus (HIV). These common viral infections are contagious.

The heme biosynthetic pathway is one of the key metabolic pathways that leads to the formation of heme from various intermediates (porphyrins and porphyrin precursors). Nearly all cells of the human body contain heme, which is essential to carry out many functions. Heme functions mainly as a small molecule that binds to proteins to form a large class of proteins called ‘hemoproteins.’ Hemoglobin is one such essential hemoprotein; it is found mainly in developing and adult red blood cells, where it functions to carry oxygen absorbed from air in the lungs to cells and tissue throughout the body. Hemoglobin also functions to carry carbon dioxide, a waste product formed by the metabolic functions of most cells, from these cells back to the lungs, where the carbon dioxide is released into the expired air and where the hemoglobin again picks up more oxygen. 

Most of the heme that is made in the human body is made in developing red blood cells, to provide for the formation of heme for hemoglobin. In the erythropoietic porphyrias, the major site of the overproduction of heme precursors is the developing red blood cells, or the bone marrow, also called erythropoietic tissue. Thus, the name erythropoietic porphyria. 

The other major organ where heme is made is the liver. When the major overproduction of heme precursors occurs in the liver, the disorder is called a hepatic porphyria.

It is not possible to provide a general or generic answer this question. This requires the thoughtful assessment of individual people by a board-certified specialist in general internal medicine, perhaps, in consultation with selected sub-specialists and porphyria experts.

This depends upon the specific type of porphyria and the severity. For most people, the life expectancy is similar to that of persons without porphyria. In the case of people with acute hepatic porphyrias, especially those with chronically high levels of the porphyrin precursors ALA and PBG, there are increased risks of the development of high blood pressure, chronic kidney disease, and, usually later in life (after age 50) the development of hepatocellular carcinoma (primary liver cell cancer).These conditions can be treated successfully, so people with acute porphyria should be screened on a regular basis for the development of these complications. If they are found, they should be treated and controlled. 

People with EPP or XLP generally have a life expectancy similar to those without porphyria. An exception may be those who also develop liver failure. People with PCT have a life expectancy similar to those without porphyria. The life expectancy of people with CEP is not known.

For most people with porphyria, there is no contraindication to their having children. 

Women with an acute porphyria are more prone to have acute attacks during pregnancy and in the post-partum period, and these may require prompt and careful treatment. Such pregnancies are best monitored by an ob-gyn specialist with expertise in high-risk pregnancies. 

The risk for people with porphyria having a child also affected depends on the type of porphyria. Please see the United Porphyrias Association website for detailed information on the inheritance of each type of porphyria.

There are different treatment options available for acute and cutaneous porphyrias.

Acute Porphyrias

Treatment for acute attacks requiring hospitalization is hemin (panhematin) which is given intravenously. During hospitalization, people typically get one dose a day for about four days. In addition to hemin, people may need intravenous fluids, medications to control nausea, high blood pressure, and pain. 

People who have recurrent (frequent) attacks may sometimes be recommended hemin infusions as an outpatient. This can be given on a regular schedule or when a patient is in early stages of an attack. 

Givlaari (Givosiran) is a drug approved for people with acute hepatic porphyrias. It was tested in people with recurrent attacks (> 4 attacks/year) to prevent attacks. Givosiran has not been tested for the management of acute attacks in the hospital. 

In addition to these, people with acute porphyria may develop chronic symptoms and may need medications to control pain, nausea, and other symptoms. 

The choice of therapy may depend on the symptoms and should be made by the treating physician after a complete evaluation. 

Cutaneous Porphyrias

There are different types of cutaneous porphyrias and the treatment varies by type. 

EPP/XLP: The primary mode of symptom management for EPP/XLP patient has been sun avoidance. Medications such as beta-carotene, cysteine, vitamin C, and others have been tried however there is no clear evidence that any of them are effective. 

Scenesse (Afamelanotide) was approved by the FDA for the treatment of EPP/XLP in adults. This drug is administered in the subcutaneous tissue (just below the skin) generally around the belly area through a large needle after numbing the area. The implant is administered once every two months and it dissolves by itself. It works by increasing the amount of melanin in the skin which makes the skin darker. Studies show that people with EPP/XLP taking this drug can spend longer time in the sun without pain. Currently there is no FDA approved treatment for children with EPP/XLP. 

Other medications are currently in clinical trials for adolescents and adults with EPP/XLP. 

CEP: CEP is an extremely rare disorder and the symptoms are very variable. Some people may require a bone marrow transplant, others may need ongoing blood transfusions and other supportive care. In addition, people should avoid the sun to prevent symptoms and blister formation which can be very severe. 

PCT: PCT is one of the most common porphyrias. The primary treatment is phlebotomy (bloodletting) until the blisters disappear and the urine and blood tests normalize. In addition, there is an oral medication, chloroquine (or hydroxychloroquine), which can be used to control symptoms. In all cases of PCT, it is important to treat the underlying factor contributing to the disease manifestations such as hepatitis C, HIV, excessive alcohol consumption, etc. 

It is important to remember that all people respond differently to medications and treatment should be individualized to the person.

Treatment during pregnancy should be administered only after careful evaluation of risks and benefits. For the acute porphyrias, hemin has been safely used during pregnancy and does not appear to impact the fetus. 

Givlaari has not been tested in pregnant women and should not be used in people who are pregnant or planning a pregnancy. 

Scenesse has also not been tested in pregnant women and should not be used during pregnancy.

For people with an acute porphyria, it is important to have a healthy, well-balanced diet and avoid fasting or dieting. Excessive carbohydrates are not recommended routinely. There are no specific recommendations for vitamins or supplements. 

People with cutaneous porphyrias can have low vitamin D levels as they avoid sunlight. Daily vitamin D supplements are recommended to maintain bone health.

Individuals with a disease-causing change in one of the acute porphyria genes without symptoms have "latent" acute porphyria. However, this does not mean that they will never have symptoms. Exposure to certain environmental factors, such as medications, can greatly influence whether an individual with a porphyria-causing gene change has symptoms. This is why it is important that all family members of individuals diagnosed with acute porphyria be tested, whether they have symptoms or not, and that all individuals who have a confirmed diagnosis of acute porphyria be educated about and follow the recommended precautionary and preventive measures.

Yes! The diagnosis of acute porphyria is always an important piece of medical information, even when there are no symptoms. It may, for example, influence the choice of medications to treat other conditions, the choice of anesthesia for surgery, or dietary recommendations.

Surgery and pregnancy may increase the risk of an acute porphyria attack. This risk can be greatly reduced if certain precautions are taken, including the type of anesthesia used in surgeries. The surgeon and anesthesiologist should consult a porphyria expert prior to hospitalization for surgery. Such consultation may also be helpful during pregnancy. Attacks of acute porphyria can occur during pregnancy. Treatment of acute attacks during pregnancy is also possible.

For information about safe and unsafe drugs in the acute porphyrias, it is best to consult the European Porphyria Network. The database contains expert assessments of the potential of drugs to provoke attacks of acute porphyria (AIP, VP, HCP & ADP) based on the available evidence. However, this evidence is not always complete, which may lead to some degree of uncertainty. The information in this database is meant as guidance to health care professionals. It must be made clear that the prescription of drugs to a patient with acute porphyria is entirely at the risk of the physician in charge. 

Since most commonly used drugs have not been tested, they should be avoided if at all possible. If a question regarding drug safety arises, a physician or medical center specializing in porphyria should be contacted.

Yes, males and females are equally at risk for having acute porphyria. Exposure to certain environmental factors, such as drugs, chemicals, and diet, greatly influence whether an individual - men and women - with a change in a porphyria-causing gene has symptoms and the severity of symptoms. However, one of the environmental factors is hormones, and, therefore, acute attacks are more common in women. Women may experience cyclical acute attacks associated with their menstrual cycle, starting in puberty. Such attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high.

People with an acute porphyria should have a healthy balanced diet. Fasting for long periods of time and dieting should be avoided.

Thinking and memory can be affected when someone is having an acute attack. Someone with acute porphyria may also experience some neurological effects, including confusion, convulsions, muscle weakness, and, rarely, paralysis, due to effects on the nervous system from an acute attack. The effects of acute porphyria on long term thinking and memory are not known.

An acute attack can be brought on by certain drugs, hormones in women, environmental factors including chemicals of various types, nutrition including fasting and low carbohydrate diets, alcoholic beverages, medical and physical stress, and physical fatigue. Many times, the trigger of an acute attack is unknown.

Flu shots are okay to take for people with acute porphyria, and can be taken safely. Any immunizations also appear to be okay. In fact, since other illnesses can bring on an acute attack, remaining healthy is one of the most important ways to prevent acute attacks. 

There has been no information to date to suggest that CAT scans with or without contrast agents should not be performed on an individual with acute porphyria.

Drugs on the “unsafe” list are those drugs that should be avoided by individuals with an acute porphyria because they have been found to provoke an acute attack in some individuals. If a drug prescribed for an individual diagnosed with an acute porphyria is on the “unsafe” list, the prescribing physician should check the Drug Database for a safe alternative. No drug should be withheld if it is judged essential for optimum treatment of a life-threatening condition (e.g. chemotherapy for cancer). The risk versus the benefit should be assessed and discussed with the patient. For help with this assessment you may wish to contact a Porphyria expert. It may be recommended that a person undergo biochemical monitoring (i.e., ALA and PBG levels) in the early stages of treatment. It must also be noted that response to drugs in people with an acute porphyria is extremely variable and individuals may be encountered who have used an unsafe drug without adverse effect.

Donation of blood might not be harmful to you if you are in good health and have not had a recent attack. Your blood would also not be harmful to a recipient. However, a blood bank might have a policy of not taking blood from anyone with a chronic condition, just to be on the safe side.

Acute porphyrias are liver disorders, so your liver should not be donated, because the recipient would be likely to develop acute porphyria. Because acute porphyrias can damage the kidneys, you should probably not be a living kidney donor, and losing a kidney would reduce your reserve kidney function. A transplant program might have a policy of not transplanting certain organs from anyone with a chronic condition, just to be on the safe side. But transplanting some tissues, such as skin and cornea, should not be a problem.

This may be as short as a few days, but is highly variable. Multiple triggers may be present, so the timing of symptoms cannot be predicted.

Attack symptoms are nonspecific and can be mimicked by many other medical conditions. If an individual has been diagnosed already as having acute porphyria, the diagnosis of an acute attack is based on the symptoms and physician judgement. The levels of porphyrin precursors (porphobilinogen [PBG] and aminolevulinic acid [ALA]) are not determining factors because these often remain high between attacks. However, levels of ALA and PBG generally do spike during acute attacks.

If you are vomiting, have severe pain, seizures, or other neurological symptoms, it is often best to go the ER.

Yes. A seizure can be due to effects of acute porphyria on the brain, or be a consequence of decreased sodium in the bloodstream, which is a complication of the attack. Seizures generally indicate that the attack is severe and requires medical attention as soon as possible.

Attacks cause increases in the heart rate and blood pressure, due to effects on the autonomic nervous system, and these will generally return to normal with treatment of the attack. People with acute porphyria may develop chronic hypertension, which needs to be managed in the usual manner.

Your doctor can advise on managing your diabetes using pills and/or insulin. A dietitian is also helpful for designing a diet with the proper amounts of carbohydrate and fat.

Premenstrual attacks are likely due at least in part to the high levels of progesterone that occur during the second half of the cycle. If these are frequent, and no other factors are contributing, such attacks may be prevented using a GnRH analogue (e.g. Lupron) or Givlaari. You should discuss these treatment options with your doctor and a porphyria expert. Removal of the ovaries is not considered unless there are other medical indications and the patient is interested in permanent sterilization.

Yes. Other conditions that decrease food intake or cause fever and metabolic stress can trigger an attack.

This is not indicated if a healthy diet containing all required nutrients is maintained. A multivitamin tablet containing the daily requirements is not harmful, however.

It may be best to consult a dietitian to be sure you get an adequate amount of all required nutrients. A vegetarian diet generally will contain adequate amounts of carbohydrates and fiber, but may be low in protein, some vitamins and minerals such as iron and zinc.

Checking levels of urine porphobilinogen and aminolevulinic acid at least yearly is advisable to have some idea how active your acute porphyria is.

Sun sensitivity is the main symptom in CEP, EPP, XLP, and PCT. VP and HCP, which are acute porphyrias, can also have blistering sun sensitivity. The degree of sensitivity to sunlight varies considerably. People with sun sensitivity have high levels of porphyrins in the blood plasma which, depending on the type of porphyria, have originated from the liver or the bone marrow. Ultraviolet light interacts with porphyrins in such a way as to damage skin tissue. In general, for people with CEP, EPP, XLP and PCT they should protect themselves from sun exposure. For people with VP and HCP, only if they have sun sensitivity do they need to protect themselves from sun exposure.

Most people with a cutaneous type of porphyria must learn to avoid sunlight as much as possible. Transparent topical sunscreens which block ultraviolet light are ineffective. Physical sunscreens (e.g., zinc oxide) maybe helpful. 

Protective clothing may also be recommended.

People with EPP and XLP experience photosensitivity that starts in infancy or early childhood and is characterized by pain, redness, and itching of sun exposed skin. The time after sun exposure to onset of symptoms is variable among people. Variegate porphyria and rarely hereditary coproporphyia (both acute hepatic porphyrias) can also experience photosensitivity that manifests differently than in EPP and XLP and analogously to porphyria cutanea tarda (a hepatic cutaneous porphyria) with skin friability and blistering skin lesions on sun exposed areas. 

The photosensitivity in porphyria is to light in the blue-violet spectrum of visible light (VIBGYOR - violet, indigo, blue, green, yellow, orange, red). The peak wavelength for light-mediated porphyrin excitation is ~ 410 nm. Indoor light sources (including lights for surgical or dental procedures) that emit within this spectrum can be problematic. 

Yellow filters (which omit wavelengths below ~ 470 nm) can be used to protect people if needed. Fluorescent bulbs have little light within this spectrum and typical LED lights used for lighting purposes also lack within this spectrum.

Avoidance of sun exposure, including through windows, is the most effective way of preventing photosensitivity reactions. Clothing which blocks exposure to visible light may provide some protection as well as hats, gloves, etc.

Monitoring for liver complications is recommended. Treatment of severe liver complications (cholestatic liver failure) requires specialty care at a center with expertise in EPP and XLP and with liver and bone marrow transplant expertise. 

Synthesis of vitamin D by the skin in response to exposure to ultraviolet light (in sunlight) is the major source of this vitamin. As a consequence of avoiding sunlight, people are therefore at risk for vitamin D deficiency and may require supplementation. 

Mild anemia, with laboratory studies suggestive of iron deficiency, are observed in some people. It remains unknown whether iron therapy improves the anemia in this setting and/or may worsen photosensitivity.

A person's sensitivity to light is dependent on the light quality, the duration of exposure, and individual factors (including geographic latitude and altitude, natural skin pigmentation, and other factors which are not fully understood).

In EPP and XLP, the source of the majority of the phototoxic substances that cause symptoms originate from red blood cells and their parent cells in the bone marrow. Thus, bone marrow transplantation from a donor who lacks EPP or XLP is curative for the recipient. As bone marrow transplantation is associated with significant risk to people (including death and potentially multiple life-altering complications), it is reserved for a very rare subset of people for whom the benefit is thought to out weight the risks of this procedure.

For the acute pain of a severe phototoxic reaction, as may occur in EPP or XLP, the key is avoidance of any further sun or strong light exposure and the use of ice packs/cold compresses on the most severely affected areas of the skin. Some people seem to benefit from a short course of potent, anti-inflammatory medication, such as prednisone or methylprednisolone (Medrol dose pak). Others may derive some benefit from a combination of H1 [diphenhydramine (Benadryl)] and H2- [cimetidine [Tagamet], famotidine (Pepcid)] antihistamine blockers or from combination histamine and serotonin blockade with cyproheptadine [Periactin].