Understanding Porphyria

  • Porphyria is a family of 8 disorders related to the way your body makes heme- an important molecule for the body. When there is an error in the pathway to make heme, the building blocks of heme- called porphyrins and porphyrin precursors- build up in the body and cause porphyria symptoms.

    Each step of making heme is done by an enzyme. Depending on which enzyme isn’t working properly, different porphyrins and porphyrin precursors will build up and cause the different types of porphyria.

  • Most types of porphyria are genetic, which means they are inherited from a parent. However, not everyone with a gene for porphyria will have symptoms. This means porphyria can be passed down for many generations without anyone getting sick.

    Porphyria Cutanea Tarda (PCT) can be genetic or can be induced by other factors including hepatitis C infection, HIV, oral estrogens, excessive alcohol use or iron overload.

  • The overall prevalence of porphyria isn’t known- estimates range from 1 in 500 to 1 in 50,000. It is hard to get a good estimate because porphyria isn’t always recognized and diagnosed, and not everyone with a porphyria gene mutation will show symptoms.

    The different types of porphyria occur at different frequencies. For example Acute Intermittent Porphyria (AIP) is the most common type of acute hepatic porphyria- about 80% of cases- while there are less than 15 documented cases of ALAD-deficiency porphyria (ADP) worldwide.

    There are populations who are known to have a higher prevalence of porphyria due to a founder effect. For example, South Africans of Dutch descent have a higher prevalence of Variegate Porphyria, and there is a higher prevalence of Acute Intermittent Porphyria in Sweden and Nova Scotia.

  • There are eight steps to making heme. This means that there are at least eight different types of porphyria- one for each step. Each of the eight steps is done by a different enzyme, and each enzyme is encoded by a different gene.

    Some types of porphyria have similarities, so they are often grouped together. A common way of grouping them is by their primary symptoms:

    ACUTE HEPATIC PORPHYRIAS

    • Characterized by attacks that affect the nervous system.

    • Symptoms can include severe abdominal pain, nausea, vomiting, numbness or limb weakness, insomnia, anxiety, elevated heart rate, hallucinations and seizures

    • Some types of acute porphyria may have skin symptoms (blistering, pain) when skin is exposed to sunlight

    CUTANEOUS PORPHYRIAS

    • Characterized by painful reactions when skin is exposed to sun

    • Symptoms for most types include blistering lesions and fragile skin

    • EPP/XLP reactions cause pain and swelling, but not blisters

    Porphyrias are also sometimes grouped by where in the body the porphyrins first start to accumulate- either in the liver (hepatic) or the bone marrow (erythropoietic).

    It is important to remember that porphyrias are complex disorders- some acute porphyrias will also have skin symptoms, and skin porphyrias can impact the liver.

  • Porphyria can be diagnosed using either biochemical or genetic tests.

    BIOCHEMICAL TESTING

    Biochemical tests involve measuring the levels of porphyrins and porphyrin precursors in samples of urine, blood and feces. Each type of porphyria will have a distinctive pattern of porphyrins and precursors that makes it possible to identify the type of porphyria. Biochemical testing is the most common way to identify and diagnose porphyria. For the acute porphyrias, biochemical tests are considered the gold standard for diagnosis.

    While these tests are robust and accurate, collecting and preparing samples properly prior to analysis is important to prevent possible false negative results. For example:

    • The sample must be protected from light (eg. wrapped in foil) and kept cold (refrigerated or frozen). You may need to insist the sample is wrapped up. Exposure to light can cause the porphyrin molecules to break down before the sample is tested.

    • Porphyrins are present and elevated around the time you have symptoms. It is important that samples are taken during, or within 2 – 3 weeks, after an attack/symptoms.

    It is important to collect the proper sample types, which may include blood, urine and/or a fecal sample. Information on the specific tests for each type can be found here:

    It is essential that when arranging to have these tests ordered that the requesting doctor consult with the laboratory to ensure that the proper tests are ordered and available. Please contact us to find the lab closest to you that performs this testing.

    GENETIC TESTING

    Some types of porphyria are caused by genetic mutations, so it is possible to diagnose some porphyrias using genetic (DNA) testing. Testing is done by taking a blood or saliva sample. The DNA in the sample is then extracted and analyzed for mutations in the gene(s) related to porphyria.

    Genetic testing is normally available in Canada if a close family member has already been diagnosed. The diagnosed relative will be tested first so that the specific gene mutation causing their porphyria can be identified. Family members can then be tested to see if they have the same gene mutation. Please contact us for information on accessing genetic testing.

    Genetic testing in Canada is not usually done without a confirmed diagnosis in a close family member because there are many possible variations in gene mutations, not all of which will cause porphyria (some are harmless variations). If porphyria hasn’t been confirmed by a biochemical test and the gene mutation isn’t one that has already been identified, the results may be inconclusive.

    In some cases, genetic testing may be available through pharmaceutical companies. Private genetic testing is also available from the United States. Please contact us to learn more about these options.

  • Getting a diagnosis for porphyria can be challenging. Many doctors are not familiar with porphyria or how it is diagnosed. The symptoms can also imitate other, more common conditions, and the testing works best when there are symptoms present.

    Here are some steps to take if you suspect porphyria:

    KEEP TRACK OF YOUR SYMPTOMS

    Keep a record of your symptoms: when (date and time) they happen, what they were, how long they lasted and their location in your body. Your notes can help your doctor understand what you’re going through and point towards a possible diagnosis.

    CHECK IF THERE IS A FAMILY HISTORY

    If you’re able, check with your family to see if any relatives have (or had) a diagnosis of porphyria or a history of illnesses with similar symptoms. A family history of similar symptoms can point towards a genetic basis for your illness.

    IDENTIFY THE TYPE(S) OF PORPHYRIA YOU MAY HAVE

    The symptoms of the different types of porphyria overlap, here is a quick guide to the types of porphyria based on the most common symptom:

    TALK TO YOUR DOCTOR

    Ask your doctor to work with you to explore the possibility you may have porphyria. Many doctors are not familiar with porphyria, so you may need to provide them with information.

    Your family doctor can order diagnostic tests and provide referrals to specialists. Please contact us for more information on testing or referral.

    GET TESTED

    Testing is most accurate when you are experiencing symptoms. If you aren’t currently experiencing symptoms and your test comes back negative, you may want to talk to your doctor about getting another requisition for a test to be done as soon as you start experiencing symptoms again.

    TAKE PRECAUTIONS

    If you suspect you may have porphyria, you may want to follow the guidelines for managing porphyria to see if it helps reduce or manage your symptoms:

    • For acute hepatic porphyrias this includes avoiding known triggers- checking medications in the safe drug list, avoiding fasting and low-carb diets, and alcohol. See the full list here. Be sure to ask health care providers to check any drugs in the safe drug database before administering them and proceed with caution if they are potentially unsafe. If you believe you are having an attack, advocate for a urine test and request a glucose infusion.

    • For cutaneous (skin) porphyrias, avoid direct sunlight, including through glass. Wear dark, tightly woven clothing that covers your skin when outside.

  • Getting a diagnosis can be a relief, especially if it has taken years to get answers. Here are some next steps:

    FIND A PORPHYRIA SPECIALIST

    There are a number of different medical specialties that treat porphyria, including hematologists, internists, dermatologists and gastroenterologists. If you don’t already have a specialist, please contact us for help finding one in your area.

    LEARN MORE ABOUT YOUR PORPHYRIA

    Because porphyria is so rare, patients often have to be the expert on their condition. Learn more about your specific porphyria on this website and through our suggested links.

    We are aware of potentially dangerous information being circulated across social media platforms and on various websites regarding the diagnosis, management, and treatment of the porphyrias. If you have concerns about your care, testing or general porphyria management, please connect with a recognized porphyria specialist/expert centre or your national porphyria patient organization. Please see this statement from the Global Porphyria Advocacy Coalition.

    MAKE A PLAN TO MANAGE YOUR PORPHYRIA

    Thinking about how you will respond if/when you have symptoms can be helpful. You may want to consider:

    • Having your doctor create a care plan for emergency treatment and getting a medic-alert bracelet or card.

    • Sharing the information about your care needs with trusted family members or friends so they can help educate or advocate for you if you are unable to speak for yourself ( for example: requirements for avoiding light, appropriate care during an attack).

    • Making arrangements with schools or workplaces to avoid triggers and unsafe lights.

    • Having items on hand that can help you when you have symptoms, such as sun-protective items you can carry with you or a source of glucose.

    BECOME A MEMBER TO STAY UP-TO-DATE

    The Canadian Association for Porphyria regularly shares new research, treatments, education and connection opportunities. We encourage you to become a member, sign up for our newsletter and follow us on social media.

    CONNECT WITH OTHERS

    Having porphyria is often isolating. It can be helpful to connect, share and learn from each other's experiences. You learn about upcoming opportunities by visiting our event page, signing up for our newsletters or following us on social media.