Frequently Asked Questions
How does one get porphyria?
Most porphyrias are inherited. However, one type, Porphyria Cutanea Tarda (PCT), may either be inherited (also referred to as “familial”) or “sporadic” due to various environmental factors. In each type of porphyria there is a deficiency of a specific “enzyme”. These enzymes are involved in the synthesis of “heme”, a substance important to many body functions and are found in large amounts in bone marrow and red blood cells (which contain hemoglobin), and also has an important function in the liver and muscles. The type of porphyria present is determined by which enzyme is deficient; these enzyme deficiencies are usually inherited. Environmental factors, such as drugs, chemicals, diet, and sun exposure can, depending on the type of porphyria, greatly influence the severity of symptoms.
How are the porphyrias inherited? Can my children inherit porphyria from me?
The inherited porphyrias are either autosomal dominant (inherited from one parent), autosomal recessive (inherited from both parents), or X-linked (the gene is located on the X-chromosome). “Autosomal” genes always occur in pairs, with one inherited from each parent. Individuals with an autosomal dominant form of porphyria have one “non-working” gene paired with a “working” (or normal) gene. Each of their children has a 50% chance of inheriting the non-working gene. Some of those who inherit the non-working gene will develop symptoms. Individuals with an autosomal recessive type of porphyria have a pair of non-working genes, and each of their children will inherit one non-working gene for that porphyria which will be paired with the working gene of their partner. Such individuals are referred to as “carriers” and will not have any symptoms. If two carriers of the same autosomal recessive porphyria have children, each child will have a 25% of inheriting a non-working gene from each carrier parent, and having the disorder. Because all porphyrias are uncommon, 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 go on to develop another type. However, patients with more than one type of porphyria have been reported.
How are the porphyrias classified?
The best way to classify a case of porphyria is to determine which enzyme is deficient, or not functioning properly. Normally these enzymes act in a sequence to make heme from simpler molecules. Heme is a vital substance for all body organs and consists of an iron atom surrounded by a porphyrin molecule. If a specific enzyme is not made properly or there is not enough of the enzyme, it cannot function properly and that step in the heme-making process cannot proceed.
Sometimes other classifications are useful. Most commonly the porphyrias are divided into the “acute“ and “cutaneous” porphyrias, depending on the primary symptoms. The acute porphyrias [Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and ALA-dehydratase Deficiency Porphyria (ALD)] present with sudden attacks of severe stomach pain that last for several days; VP and HCP may also have skin symptoms. The cutaneous porphyrias present with blistering and scarring of the skin, pain, and/or redness and swelling in sun-exposed areas. The porphyrias may also be classified as “hepatic” or “erythropoietic”, depending on the organ where the porphyrins accumulate, the liver for the hepatic porphyrias [AIP, HCP, VP, Porphyria Cutanea Tarda (PCT), and Hepatoerythropoietic Porphyria (HEP)] or the bone marrow for the erythropoietic porphyrias [Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EPP), and X-Linked Protoporphyria (XLP)].
What treatment and prevention are available?
To date, there is no cure for any of the porphyrias. Treatment and prevention depends on the type of porphyria. Preventive measures, which include avoidance of certain drugs and alcohol, as in the hepatic porphyrias, and sun exposure, as in the erythropoietic porphyrias, are also important in those individuals who are identified as having inherited porphyria, even if they have never had symptoms.
For the acute porphyrias, hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required with monitoring of salt and water balance. Harmful drugs should be stopped. Attacks are treated with either glucose loading or intravenous administration of hemin (Panhematin®). Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices.
PCT, both familial and sporadic, can be treated with regularly scheduled phlebotomies (removal of blood) to lower the amount of in the liver or a low dose regimen of hydroxychloroquine as well as removal of factors (for example, certain medications) that activated the disease.
Treatment of the cutaneous porphyrias is dependant on the specific porphyria. For CEP, blood transfusions to correct anemia, splenectomy (removal of the spleen) are often needed treatments. Bone marrow transplant (BMT) has also been done in severe cases with good results. For EPP, treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance. Avoidance of sunlight (and fluorescent lights for CEP) is recommended for all individuals with a cutaneous porphyria as well as those diagnosed with HCP or VP who have porphyria-related sun sensitivity.
Is porphyria progressive or lethal?
Unlike some genetic disorders in which all individuals who inherit a gene mutation become ill,the severity of porphyria varies considerably. Such variability is due to certain “additional factors” other than the gene itself. Consequently, risks of severe medical difficulties or even death in the acute porphyrias are often diminished when affected individuals are well informed of their diagnosis and adopt suggested precautionary measures. Even with modern treatment and prevention, some patients still have repeated attacks. However, progressive deterioration and death from paralysis in the acute porphyrias are very unusual.
Should doctors be informed that an individual has porphyria, even if it is latent?
Yes! The diagnosis of porphyria is always an important item of medical information, even when there are no symptoms. It may, for example, influence the choice of drugs to treat other conditions, the choice of anesthesia for surgery, or dietary recommendations.
What diagnostic tests are available?
There are many laboratory tests available for the porphyrias, and it is often difficult to decide which should be chosen. Many of these tests are expensive. The results are often difficult to interpret. The tests vary in sensitivity and specificity. If a test is “sensitive”, it is unlikely to be falsely negative (that is, fail to diagnose porphyria in a patient who has the disorder). If a test is “specific”, it is unlikely to be falsely positive (that is, diagnose porphyria in a patient who does not have the disorder). Certain tests are both sensitive and specific in patients who have symptoms that are suggestive of a porphyria. It is advisable 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.
When abdominal and neurological symptoms suggest an acute porphyria, the best screening tests are urinary aminolevulinic acid (ALA) and porphobilinogen (PBG). When there are cutaneous symptoms that suggest porphyria, the best screening test is a plasma porphyrin assay. If one of these screening tests is abnormal, more extensive testing, including urinary, fecal, and red blood cell porphyrins, are often indicated. Urinary, fecal, and red blood cell porphyrin measurements are not very useful for initial screening because they lack either sensitivity or specificity and, therefore, are often difficult to interpret. Measurement of heme biosynthetic enzymes in red blood cells or lymphocytes is not appropriate for screening unless it is part of a family study that is done after someone in the family is already known to have a specific enzyme deficiency.
DNA testing to identify the specific mutation in an individual’s porphyria-causing gene may be indicated to confirm the diagnosis of a specific porphyria. Before requesting DNA testing, it is recommended that patients have biochemical testing (urinary, stool and/or plasma porphyrins and porphyrin precursors (ALA and PBG) and/or enzyme assays). However, many patients have not had an acute attack or are not symptomatic at present, so biochemical testing may be inconclusive.
In contrast, DNA testing is the most accurate and reliable method for determining if a person has a specific porphyria and is considered the "gold standard" for the diagnosis of genetic disorders. If a mutation (or change) in the DNA sequence is found in a specific Porphyria-causing gene, the diagnosis of that Porphyria is confirmed. DNA analysis will detect more than 97% of known disease-causing mutations. DNA testing can be performed whether the patient is symptomatic or not. Once a mutation 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.
What is “latent” porphyria? If my doctor told me that I have “latent” porphyria, does this mean that I will never have any symptoms?
Individuals with a disease-causing mutation without symptoms have "latent" porphyria. However, this does not mean that such an individual will never have symptoms. Genetic factors (that is, the presence of a porphyria-causing gene mutation is not the only factor involved. Exposure to certain environmental factors, such as drugs, chemicals, diet, and sun exposure can, depending on the type of porphyria, greatly influence whether an individual with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms. There may also be additional factors, including additional genes, that may modify the symptoms. This is why it is important that all family members of individuals diagnosed with porphyria be tested whether they have symptoms or not, and that all individuals who have a confirmed diagnosis of porphyria be educated about and follow the recommended precautionary and preventive measures for porphyria.
Where can I find a porphyria expert? What other type of doctor can diagnose me properly and what type of specialist should I see if I have porphyria.
There are several Porphyria experts in the US and outside the US, including the Porphyria Centers in this Consortium. Information about other experts can be obtained by contacting the American Porphyria Foundation (www.porphyriafoundation.com) or one of the Porphyrias Consortium members. 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.
Can I have more than one type of porphyria?
Because all porphyrias are uncommon, 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 go on to develop another type. However, patients with more than one type of porphyria have been reported.
Can porphyria improve with age?
The symptoms of porphyria do not improve with age, per se. Untreated, the symptoms and the secondary effects of long-term symptoms will get worsen over time. However, with proper diagnosis, treatment of acute attacks (in the acute porphyrias), and following recommended preventive measures, it is possible that symptoms may be lessened.
Should I be tested often? How often?
Monitoring of porphyrin levels and other follow-up testing is dependent on the type of porphyria and the medical status of the individual. It is, therefore, important that a person who has been diagnosed with porphyria be followed by a porphyria expert.
Does porphyria affect my liver? Should I have liver tests?
Liver function tests should be performed routinely on all individuals diagnosed with porphyria.
Do people have liver transplants for poprhyria?
Liver transplantation may be beneficial for individuals with end-stage liver disease as a result of porphyria.
My doctor diagnosed me with porphyria but the porphyria expert said I did not have it. Why would this happen and should I be retested?
Such a situation needs to be dealt with on an individual basis. Whether further testing is recommended depends on how the patient 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 results of the biochemical testing by a porphyria expert may determine that the results are not consistent with what is typically seen in a patient with porphyria during an attack. The results of DNA analysis may also contribute to the porphyria expert saying that it is unlikely that the patient has porphyria. DNA analysis, although considered to be the “gold standard” for diagnosis, is not perfect in that the patient may have a mutation in a part of the porphyria gene that is not analyzed by routine testing or the patient has a mutation in a porphyria gene that was not analyzed. In the event that a diagnosis of porphyria is still suspect, then it is recommended that the patient undergo additional biochemical testing at the time of an acute attack. Additionally, further testing may include DNA analysis for other acute porphyrias (if only one or two were tested).
Is porphyria research being conducted? How can I volunteer to participate in research?
Yes. For additional information about research being conducted and how to volunteer to participate, please contact either the Porphyrias Consortium Coordinator by email (email@example.com) or telephone (212-659-6779) or one of the site coordinators (see list of Porphyrias Consortium Members for locations and contact information).
Does surgery or pregnancy pose additional risks?
Porphyria-related risks of surgery and pregnancy depends on the type of porphyria. Surgery may increase the risk of an attack of the acute porphyrias. This risk can be greatly reduced if certain precautions are taken, including the type of anesthesia used. The patient’s surgeon and anesthesiologist should consult a porphyria expert prior to hospitalization for surgery. Such consultation may also be helpful during pregnancy. Although attacks of acute porphyria can occur during pregnancy, the risk appears to be less than formally thought. Treatment of acute attacks during pregnancy is feasible.
What drugs are safe and unsafe?
For information about safe and unsafe drugs in the acute porphyrias, it is best to consult the American Porphyria Foundation Acute Porphyrias Drug Safety Database (http://www.porphyriafoundation.com/drug-database) or the European Porphyria Initiative (http://www.porphyria-europe.org/03-drugs). The databases contain 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 these databases 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.
Can men have acute porphyria?
Yes. Since the acute porphyrias are inherited in an autosomal dominant pattern, males and females are equally at risk for having an acute porphyria. Exposure to certain environmental factors, such as drugs, chemicals, and diet, greatly influence whether an individual—males and females--with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms. However, one of the environmental is hormones, and, therefore, attacks are more common in women than in men. 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.
Do I need a special diet with porphyria?
Nutritional recommendations for the acute porphyrias emphasize a high carbohydrate intake as part of a balanced diet that provides all essential nutrients. The recommendations include an adequate intake of dietary fiber, vitamins and minerals. The goals are to prevent acute attacks of Porphyria that may be related to diet, avoid deficiencies of nutrients, and maintain a normal body weight. More information on diet on theAmerican Porphyria website (http://www.porphyriafoundation.com)
Will porphyria affect my thinking and memory?
Generally, the acute porphyrias do not affect thinking and memory. However, a person may experience some neurological effects, including confusion, convulsions, muscle weakness, and, rarely, paralysis, due to effects on the nervous system.
What precipitates a porphyria attack?
In an individual with an acute porphyria, 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.
I have acute porphyria: Can I do the following: take a flu shot, donate my organs, take a CAT scan with the contrast?
Flu shots are not contraindicated for individuals diagnosed with acute porphyria, and can be taken safely. Any immunizations appear to be okay. In fact, since other illnesses can bring on a porphyria 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 porphyria.
Organ donation would be up to a particular transplant program or network. In acute porphyrias any organ should be acceptable except perhaps the liver. In the case of PCT organ donation would most likely be acceptable in the absence of a history of hepatitis C or HIV.
What should I do if the drug I need is on the unsafe list?
Drugs on the “unsafe” list are those drugs that should be avoided by individuals diagnosed 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 patient undergo biochemical monitoring in the early stages of treatment It must also be noted that response to drugs in patients with an acute porphyria is extremely variable and individuals may be encountered who have used an unsafe drug without adverse effect.
Is sunlight always harmful?
Sun sensitivity can occur in all but two types of porphyria, specifically AIP and ADP. The degree of sensitivity to sunlight varies considerably. Patients 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. Some treatments may help patients tolerate sun exposure even without lowering porphyrin levels. In some cases, treatment can lower porphyrin levels and sunlight can be tolerated.
Should I use a special sunscreen?
Most patients with a cutaneous type of porphyria must learn to avoid sunlight as much as possible. Protective clothing may also be recommended. For patients with EPP, treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance but does not lower porphyrin levels. Over-the-counter sunscreens and over-the-counter beta carotene (vitamin A) is not effective.