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Friday, October 21, 2016

Accused of Being a Hypochondriac, Lisa is Finally Diagnosed with Acute Intermittent Porphyria- Global Genes

Accused of Being a Hypochondriac, Lisa is Finally Diagnosed with Acute Intermittent Porphyria

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A swollen stomach made her look pregnant, but the pain — “burning,” “shocking,” “horrible,” “out-of-this world,” as she describes it — was worse than childbirth, leaving her doubled over and gasping for breath. Symptoms came and went, seemingly at random. Vomiting. Constipation. High blood pressure. A racing pulse. Numbness in her hands. Paralysis in her right foot.
Lisa Kehrberg spent several days in a hospital, but every test came back normal. And the doctors began to wonder if perhaps she had been under a lot of stress lately.
As a physician herself — a specialist in pain management, as a matter of fact — Kehrberg knew how to translate that question: “There’s really nothing wrong with you.”
“Actually, no,” she told the doctors. She hadn’t been under stress. “I’m really sick right now. Can you help me?”
“You need to calm down,” one health-care worker told her. “Go home. Take it easy. And pull yourself together.”
Kehrberg had been sick before. The first bout came 22 years ago, when she was going to high school in Bartlesville. Another one hit during college, when she was briefly hospitalized with abdominal pain. But it wasn’t until September 2013, while she was working as a doctor for U.S. Department of Veterans Affairs in Chicago, that Kehrberg finally demanded answers.
Released from one Chicago hospital without a diagnosis, she checked into another one. Did the doctors there think she was a hypochondriac?
“Yeah, I’m sure they did,” she said. “Doctors are too quick to give up. ‘It’s stress.’ ‘It’s your imagination.’ ‘It’s not as bad as you’re saying it is.’ They don’t want to believe that there’s something wrong with you if they don’t know what it is.”
The second hospital did all the usual tests, with the same results. “Normal.” Why not try something different?
“It’s almost a cultural thing for doctors,” she said. “It’s looked down upon to start testing for rare diseases. Nobody wants to look like they’re grasping for answers. ‘It can’t be that, so it must be your imagination.’”
Kehrberg remained undiagnosed until a hospital nurse noticed that her urine had turned dark brown, a classic symptom of a rare genetic disorder called Acute Intermittent Porphyria, by some estimates afflicting less than 0.0001 percent of the population.
Kehrberg had heard of it herself but never considered the possibility. While not curable, the disease can be controlled to some extent by diet and medication.
More than a year later, Kehrberg now speaks as an advocate for people with Porphyria and other rare conditions. And she came back to Oklahoma recently for a fundraiser at her parents’ ranch near Pawhuska.
Her message to patients: “Speak up. Trust your instincts. Demand answers.”
And to physicians: “Listen to people and believe what they are telling you. There aren’t a lot of hypochondriacs walking around out there. There are a lot of sick people who need help.”

SOURCE Article by Michael Overall.

Wednesday, October 19, 2016

Important Things To Know Before The FDA Meeting For EPP On MONDAY

Important Things To Know Before The FDA Meeting For EPP On MONDAY

The FDA Meeting for EPP is just around the corner! The FDA has distributed additional information for all registered attendees. The check in process is lengthy, so everyone needs to be sure to arrive to the FDA at 9AM on Monday, October 24th. As a reminder, the APF will have a shuttle bus available to transport attendees between the Holiday Inn – College Park and the FDA.
Transportation: If you are taking a cab, ask the driver to drop you off at Building 1. If you will be driving and need to park, there will be signs labeled “Event Parking” pointing you in the direction of various surface parking lots (Southeast, 132A and 132B). Parking spots may be difficult to secure that will be close to Building 1, but there will be shuttles circulating to all parking lot bus stops every 5 minutes that can pick you up. Make sure to tell the shuttle driver to drop you off at Building 1. Here is FDA’s transportation page for more information:…/WhiteOakCampusInformation/ucm241740.htm
Arriving: Please make sure to first arrive at Building 1 in order to clear security and enter FDA as a guest. Building 1 is the first building you see when you arrive on campus, behind the circle with flags. You will need to present a government issued ID. Once in Building 1, visitors will have to go through the x-ray and magnetometer machines and then go down a corridor to the Building 31 Great Room. The meeting will be taking place here in the “Great Room,” or Rooms 1503 B and C. There is a small portion of the path between Building 1 and 31 where visitors will be outside. There are stairs and a ramp between the buildings. We will have FDA staff helping direct visitors to the meeting room.
Registration: Please plan to arrive between 9:00-9:45am. We will have sign-in sheets available on the tables inside the room. Luggage can be kept in the meeting room, either with the individual or in the back of the room. Sara and Meghana will both be in the room to help you with anything else you might need. If you have any difficulties finding the meeting room, or if there are any immediate questions you may need to ask, Meghana’s cell phone number is 772-342-1816, and Sara’s is 412-606-9445.
Lunch: There is a kiosk in the foyer of the meeting room where food and beverages are available for purchase. You can pre-order your lunch in the morning before the start of the workshop; if you choose to pre-order, your lunch will be available for pick-up inside the meeting room itself (where we are planning to keep the lights dimmed) during the lunch break.
Example of Past Meetings: We have conducted meetings similar to this one in the past. Please find a link to a similar meeting we held for psoriasis here:…/…/PrescriptionDrugUserFee/ucm470608.htm. Here you will find the webcast recording and full transcript of the meeting.
Agenda: The workshop agenda is now available on the workshop webpage:
The patient panel will kick off the discussion in the morning, and will be followed by a large-facilitated discussion with patients and caregivers from the audience. So we encourage you to share your experience during the large-facilitated discussion portion of the workshop. The workshop is in-tended to be an opportunity for FDA to hear directly from patients, and we make every effort to make sure the voice of the patient is heard.
We also encourage you to submit your comments directly to our “public docket”. This is a website through which patients living with EPP and oth-ers can share their experiences and perspectives. These comments supple-ment the input we get from the workshop. We will review all of these com-ments. To submit your comment, visit: Click on the “Comment Now” button in the top-right corner. You will be able to upload a PDF or Word version of your comments.
If you have any questions, you can contact the FDA at We are all looking forward to this workshop!

Monday, October 17, 2016

The FDA Meeting for EPP is Less Than 3 Weeks Away!

The FDA Meeting for EPP is Less Than 3 Weeks Away!
The APF is busy preparing for the upcoming EPP meeting at the FDA on October 24th, 2016.  We are very excited about the large number of attendees and hope even more people RSVP to us in the coming weeks.
When registering for the FDA meeting, there is an option to indicate if you are interested in participating in a panel.  If you have signed up to participate in the panel during the meeting, you should have received an email with a list of discussion questions from Meghana Chalasani (FDA meeting coordinator), in addition to your registration confirmation email.  These questions must be answered and returned to Ms. Chalasani.

The deadline to submit your answers for the panel has expired.

You will be notified of your panel status at least 1 week in advance of the meeting.  If you have signed up to speak at the panel, but did not receive the follow up email from Ms. Chalasani, then you are not being considered for the panel.  You must contact Ms. Chalasani to receive the questions.

**PLEASE let the APF know if you are selected for the panel.  If you are still unsure whether or not you can attend this important meeting, feel free to contact with any questions/comments you have.  We are excited to meet everyone in a few short weeks!

As a reminder, the deadline to register for the FDA Meeting in person OR via webcast is Monday, October 17th, 2016!  
If you are not registered, you cannot attend the meeting, so be sure to register ASAP!  Visit this website for registration:

"Remember....Research is the key to your cure!"

Friday, October 14, 2016

Taking Notes and Recording Your Visit

Taking Notes and Recording Your Visit~

Have you ever felt overwhelmed during a Doctor's appointment in which you received a large amount of information?  I know I have.  Perhaps you didn't ask any questions at the time even though you felt you had questions once you had time to process all of the details. 

     Your not alone.  Many patients find themselves with many unanswered questions once they have a chance to look over the printed materials and digest the information.

These tips may help you feel more informed during your next visit:

  • Write down a list of specific questions.

  • Bring someone to the appointment with you to listen, take notes, and record the visit.

  • Verbally summarize the instructions for the doctor or the nurse

  • Ask pointed questions such as: "can you please review with me again what I need to know about getting Porphyria testing done right?"

Many health care providers are using a technique called "Teach-Back" to ensure you understand what they just explained.  They may ask you open ended questions rather than just expecting a yes or a no response.  This is an opportunity for you to recap what you just heard which helps to reinforce the information.

                   Have fun trying this new technique at your next Doctor's appointment! 

                                                          "Remember....Research is the key to your cure!"

Wednesday, October 12, 2016

Your Stories

YOUR STORIES- Are you a porphyria survivor or know someone with an inspiring story to tell? How has porphyria affected you or your loved ones?
Whether it's a story, a poem, a picture, fundraising event, a picture or a painting, share YOUR story in your way.
Your story will be made available in a published blog and the upcoming 2017 Porphyria Awareness Week. Please email me your type & name with what you want to share

Wednesday, October 5, 2016

A journey to successful protection with Scenesse. #SuccessWithScenesse

A journey to successful protection with Scenesse.
Our son, JT von Seggern has Erythropoietic Protoporphyria, EPP. EPP negatively effects the liver, results in vitamin D deficiencies and causes excruciating pain – all from exposure to the sun. JT has experienced the painful effects of EPP since he was 2 years old. It took us 9 years of extensive research and numerous doctors’ visits, including a trip to Johns Hopkins to finally get a diagnosis for what was causing our child so much pain. While gaining a diagnosis was a huge relief, learning that there were no treatments and no cure for EPP quickly knocked the air out of our initial relief. Exactly how does one go about protecting their now 11 year old, sports loving son, from exposure to the sun?
Through the ensuing years, JT experienced frequent pain, swelling, scarring, missed school days, and numerous rounds of Prednisone to bring down the swelling caused from exposure to the sun. Flash forward to the spring, 2015. The years of dealing with EPP and the understandable anxiety that accompanies such a cruel disease started to really take a toll on JT. By the time we picked him up from college at the end of the spring semester, it was agonizingly apparent that this cycle could not continue.
In May, 2015, we asked Dr. Silverman, the doctor treating JT if there were any new developments in treating EPP. There were none in the U.S. but Dr. Silverman mentioned a promising drug containing afamelanotide. I indicated that I wanted JT on that drug and while Dr. Silverman was sympathetic to JT’s plight, he informed us that it would be next to impossible to get access to the drug for JT.
At that point, the mama bear in me went into full fight mode to protect. Through a miraculous array of previous untraveled avenues, a happenstance meeting in New York, calls to Australia, Italy the U.K. and finally a contact in Zurich.
12, 670 miles traveled
2 cab rides
2 Trams
1 hotel
1 hospital
1 implant
2-3 months of vital protection
JT received his first implant of Scenesse in Zurich, Switzerland on August 11, 2015.
The protection that JT received from this first implant of Scenesse was nothing short of miraculous and life changing. A whole new world has opened up for JT. He only missed one day of classes due to over exposure, his grades went up across the board, and he gained back his confidence and left anxiety in the dust of his shadow.
…a shadow that was made possible by the successful protection from Scenesse.
The journey to successful protection with Scenesse is not an easy one, but it is the only option available until the FDA accelerates approval for afamelanotide 16 mg.
As we pulled up to Dulles Airport for JT’s second
implant scheduled for January 12, 2016, a
beautiful rainbow greeted us and we knew we
continued to be on the right path.
JT was all smiles as we awaited our flight to Zurich
We arrived in Zurich at 7:55 am on Monday the 11th.
JT rested up and prepared himself mentally for the procedure.
The hospital is just up the hill from the Tram station and off we trekked to Pavillion F in the hospital where the implant would take place. We were MUCH better at navigating this adventure since we had done this during our first trip in August.
Tuesday morning we arose early, ate and walked a few blocks to the closest Tram station and took the #14 to Triemli Hospital
After we arrived at the
designated spot, we
waited for JT to be called
into the procedure room.
The numbing patch that Dr. Minder had given me in August to apply to JT’s side did not totally numb him so after cleaning his side with iodine, Dr. Minder gave him an injection to thoroughly numb the area.
JT was called into the procedure area where we met with Dr. Minder and her assistant. Dr. Minder went over the procedure and then she prepped JT for the implant.
Next up, the actual implant! After it was all done and JT was bandaged up, JT rested for a bit just to make sure he was fine to make the trek back to the hotel.
Knowing Scenesse was in his body and would soon be protecting him from the sun made even this rainy Tuesday one full of hope and promise. Singing in the rain was not out of the question! 
We walked back to the #14 Tram for the 20-minute ride back to the stop near our hotel.
JT rested the rest of the day.
Dr. Minder, Rocco Falchetto and Jasmin Barman joined us for a send off dinner. Both Rocco Falchetto and Jasmin Barman are EPP patients as well and being successfully treated with Scenesse.
After a good nights rest, we left our hotel and boarded our flight back to Virginia.
12, 670 miles traveled
2 cab rides
2 Trams
1 hotel
1 hospital
1 implant
2-3 months of vital protection
12, 670 miles traveled
2 cab rides
2 Trams
1 hotel
1 hospital
1 implant
2-3 months of vital protection
JT’s confidence knowing he is protected from pain for another 2 months shows on his face!
My question is, why? Why must we as American citizens go to such lengths to provide successful, safe protection from the sun? Accelerated approval for Scenesee (afamelanotide 16mg) is needed NOW. No EPP patient should be needlessly suffering.
FDA, Approve Scenesse
All this will be repeated again on March 8 for JT’s 3rd implant of Scenesse.
The lengths to which one will go through to protect their child are incredible.
And no EPP patient should have to endure all of this to live a pain free, healthy life.

Thursday, September 29, 2016

Do you know about EPP or XLP

Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP)

Erythropoietic Protoporphyria (EPP) or Protoporphyria
Erythropoietic Protoporphyria is characterized by abnormally elevated levels of protoporphyrin IX in erythrocytes (red blood cells) and plasma (the fluid portion of circulating blood), and by sensitivity to visible light that is usually noticed in early childhood and occurs throughout life.  EPP can result either from mutations of the ferrochelatase gene (FECH), or less commonly the delta-aminolevulinic acid synthase-2 gene (ALAS2).  When EPP is due to an ALAS2 mutation it is termed X-linked protoporphyria (XLP), because that gene is found on the X chromosome. 
Protoporphyrin accumulates first in the bone marrow in EPP, and then in red blood cells, plasma and sometimes the liver. Protoporphyrin is excreted by the liver into the bile, after which it enters the intestine and is excreted in the feces. It is not soluble in water so is not excreted in the urine. 
EPP is the third most common type of porphyria, and the most common in childhood.  It causes very painful photosensitivity and can greatly impair quality of life.  Delay in diagnosis is greater than with any other type of porphyria. 
Swelling, burning, itching, and redness of the skin may appear during or after exposure to sunlight, including sunlight that passes through window glass. This can cause mild to severe burning pain on sun-exposed areas of the skin.  Usually, these symptoms subside in 12 to 24 hours and heal without significant scarring. Blistering and scarring are characteristic of other types of cutaneous porphyria but are unusual in EPP.  Skin manifestations generally begin early childhood and are more severe in the summer.
There is an increased risk of gallstones, which contain protoporphyrin. Excess protoporphyrin can also cause liver damage.  Less than 5% of EPP patients’ severe liver damage and a condition caused protoporphyric hepatopathy that sometimes requires liver transplantation. 
Diagnosis and Genetic Counseling
EPP should be suspected in anyone with non-blistering photosensitivity especially when it is prolonged and beginning in childhood.  It is easy to make a diagnosis, or rule it out, once it is suspected. 
The diagnosis of EPP is established by finding an abnormally high level of total erythrocyte protoporphyrin, and showing that this increase is mostly free protoporphyrin rather than zinc protoporphyrin.  There is considerable confusion about which test to order.  Sometimes laboratories have measured only zinc protoporphyrin and reported results incorrectly as “protoporphyrin” or “free erythrocyte protoporphyrin (FEP)”.  Laboratories that measure total erythrocyte protoporphyrin, free protoporphyrin and zinc protoporphyrin and report results reliably are:
  • Porphyria Laboratory and Center, University of Texas Medical Branch at Galveston, 1-409-772-4661
  • Mayo Medical Laboratories, 1-800-533-1710 
  • ARUP Laboratories

Porphyrins are almost always elevated in plasma in EPP, but may be normal in mild cases.  Fecal porphyrins may be normal or increased. 
An experienced biochemical laboratory can usually distinguish between patients with EPP and XLP, because the former have much less zinc protoporphyrin in their erythrocytes.  This can be explained because in the marrow the enzyme ferrochelatase not only normally makes heme (iron protoporphyrin) from protoporphyrin and iron, but can also make zinc protoporphyrin, especially when excess protoporphyrin is present or iron is deficient.  However, this does not replace DNA studies. 
Rarely, EPP develops in adults in the presence of a bone marrow disorder such as polycythemia vera, and is due to expansion of a clone of red blood cell precursors in the marrow that is deficient in ferrochelase. 
DNA studies are important for confirming the diagnosis of EPP and XLP and for genetic counseling.  This should be completed first in a person known to have the disease, and the information about the mutations in that individual used to guide testing of family members. 
When EPP is due to a FECH mutation the inheritance is described as autosomal recessive.  It is most common to find that one severe mutation is inherited from one parent and another weak mutation inherited from the other parent.  The weak mutation is quite common in normal Caucasians, rare in Blacks and even more common in Japanese and Chinese populations.  This mutation is sometime referred to as “hypomorphic” because it results in formation of a less than normal amount of ferrochelatase.  But is does not cause EPP unless it is paired with a severe mutation.  The severe mutation is characteristic for an EPP family and is present in all affected individuals.  “Carriers” of the severe mutation are not affected because they do not have the weak mutation.  Affected individuals and unaffected carriers can transmit the severe mutation to the next generation.  Some of their children will have EPP if the other parent has a copy of the weak mutation.  Rarely, the weak mutation is absent in an EPP family and two severe mutations are found, with at least one producing some ferrochelatase. 
In XLP, mutations of the ALAS2 gene, which is found on the X chromosome, causes an increase in the production of the enzyme ALAS2 in the bone marrow.  Several of these “gain of function” mutations have been described in different XLP families.  In XLP protoporphyrin production exceeds that needed for heme and hemoglobin formation.  Like hemophilia and other X linked genetic diseases, XLP is more common in men.  Women have two X chromosomes and are usually not affected because they have a normal as well as a mutated ALAS2 gene.  Men have only one X chromosome and will be affected if they inherit an ALAS2 mutation.  Women with an ALAS2mutation will, on average, pass that mutation to half of their daughters (who will usually be unaffected carriers) and to half of their sons (who will be affected). 
Treatment and Management
1.  Sunlight protection
Protection from sunlight is the mainstay of management of EPP, and this is necessary throughout life.  Disease severity and porphyrin levels in erythrocytes and plasma probably remain high and relatively constant throughout life in EPP.  However, this has been little studied and more longitudinal observations are needed.  Life style, employment, travel and recreation require adjustment in order to avoid painful reactions to sunlight and even from exposure to fluorescent lighting.  For these reasons EPP can substantially affect quality of life. 
Protective clothing, including broad-brimmed hats, long sleeves, gloves and trousers (rather than shorts), is beneficial.  Several manufacturers specialize on clothing made of closely woven fabrics for people with photosensitivity. 
2.  Beta-Carotene (Lumitene Tishcon)
Beta-carotene is an over the counter product that was originally developed in a purified form as a drug for the treatment of EPP, and was shown to be effective by Dr. Micheline Mathews-Roth at Harvard University and others.  The pharmaceutical grade formulation is now distributed by Tishcon as Lumitene, and can be ordered by calling 1-800-866-0978 or via the website  Other products are less standardized and reliable and are not recommended. 
Beta-carotene provides protection by quenching reactive oxygen products that form when protoporphyrin is activated in the skin by light.  It is important to take an amount that is adequate to be protective.  For more information about Lumitene, including a recommended dosing schedule, please see the Lumitene section of this website.

3.  Other considerations
In an occasional patient, protoporphyrin causes liver problems, so monitoring liver function is important. EPP patients should also not use any drug or anesthetic which causes cholestasis (slowing down bile flow), and should also avoid alcohol. Women should avoid medications containing estrogen (birth-control pills, hormone replacement therapy), and men should avoid testosterone supplements, as these substances can also have deleterious effects on the liver of a person with EPP.
Consult a specialist.  Because EPP is a rare condition, most physicians are not knowledgeable about it.  Contact The American Porphyria Foundation, 713-266-9617 for contact with an expert and to provide further information.  A Medic Alert bracelet with instructions to contact a specialist if needed is a worthwhile precaution.
Yearly monitoring.  Testing to include erythrocyte total protoporphyrin, plasma porphyrin, complete blood counts, ferritin and liver function tests should be done yearly.  Porphyry levels are expected to be stable and liver tests to remain normal.  EPP patients may have evidence of iron deficiency, and an iron supplement may be advisable if the serum ferritin is below about 20 ng/mL. 
Vitamin D.  Because they avoid sunlight, EPP patients are likely to be deficient in vitamin D.  A vitamin D supplement with calcium is recommended for bone health. 
Liver protection.  It is important to avoid other causes of liver disease that might promote the development of liver complications from EPP.  Patients should avoid alcohol and other substances that might damage the liver, including many herbal preparations, and be vaccinated for hepatitis A and B. 
Surgical lights. Strong operating room lights can cause photosensitivity of the skin and even surfaces of internal organs.  Flexible membrane filters, such as CL5-200-X from Madico Co., are available to cover surgical lights and offer some protection.  This is especially important in EPP patients with liver failure, which causes even greater increases in protoporphyrin levels and photosensitivity. 
Drugs.  Drugs that are harmful in other porphyrias are not known to make EPP worse, but are best avoided as a precaution.  This may include estrogens and other drugs that might reduce bile formation.  A short course of a non-steroidal anti-inflammatory drug can provide some pain relief after an episode of photosensitivity, but can cause ulcerations of the digestive track especially with prolonged use. 
Laser treatment.  According to Dr. Roth, laser treatments for hair removal or eye surgery have not been a problem in EPP people.  But the doctor should be made aware of the diagnosis, and that laser output between 400 and 650 nanometers might be harmful. Before hair removal treatment, the doctor may irradiate a small area of the skin to be treated for the length of time it will take to do the hair removal to ascertain if the patient would react within the period of time that a reaction to sunlight would be expected in that patient.  
Children with EPP.  Avoiding sunlight can be difficult for children with EPP who have less sunlight tolerance than their friends.  Camp Discovery is an option for such children.  It provides a week-long summer camping experience of fishing, boating, swimming, water skiing, arts and crafts, and just plain fun for young people with skin disorders, and is sponsored by the American Academy of Dermatology.  Full scholarships, including transportation, are provided by the American Academy of Dermatology through generous donations of their members and other organizations. Members of the Academy are asked to recommend candidates for Camp Discovery, so ask your child's doctor about sending your child to Camp Discovery.
Clinuvel Pharmaceuticals is developing afamelanotide (Scenesse®) for the treatment of EPP.  This drug is given by injection and increases skin pigmentation.  Another study of this drug is expected to open within the next year. 
All patients with porphyria are encouraged to enter the Porphyrias Registry at the Porphyrias Consortium website.  A link to this website is found on the website of the American Porphyria Foundation.  Registration demonstrates to NIH that patients and their families think that research on porphyrias is important.  You can also ask that one of the 6 porphyria center in the Consortium contact you.  

Additional Reading about EPP and below that is more info on XLP:
Erythropoietic Protoporphyria
NORD gratefully acknowledges Micheline M. Mathews-Roth, MD, Associate Professor of Medicine, Harvard Medical School, for assistance in the preparation of this report.
Synonyms of Erythropoietic Protoporphyria
  • EPP
  • Erythrohepatic Protoporphyria
  • Protoporphyria
General Discussion
Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disorder characterized by a deficiency of the enzyme ferrochelatase (FECH). Due to abnormally low levels of this enzyme, excessive amounts of protoporphyrin accumulate in the bone marrow, blood plasma, and red blood cells. The major symptom of this disorder is hypersensitivity of the skin to sunlight and some types of artificial light, such as fluorescent lights (photosensitivity). After exposure to light, the skin may become itchy and red. Affected individuals may also experience a burning sensation on their skin. The hands, arms, and face are the most commonly affected areas. Some people with erythropoietic protoporphyria may also have complications related to liver and gallbladder function. Erythropoietic protoporphyria is inherited as an autosomal dominant genetic trait with poor penetrance.
Erythropoietic protoporphyria is one of a group of disorders known as the porphyrias. The porphyrias are all characterized by abnormally high levels of particular chemicals (porphyrins) in the body due to deficiencies of certain enzymes essential to the synthesis of hemoglobin. There are at least seven types of porphyria. The symptoms associated with the various types of porphyria differ, depending upon the specific enzyme that is deficient. It is important to note that people who have one type of porphyria do not develop any of the other types.
Signs & Symptoms
The most common symptom of erythropoietic protoporphyria is hypersensitivity of the skin to sunlight and some types of artificial light (photosensitivity), with pain, itching, and/or burning of the skin occurring after exposure to sunlight and occasionally to fluorescent light. Affected individuals may also exhibit abnormal accumulations of body fluid under affected areas (edema) and/or persistent redness or inflammation of the skin (erythema). In rare cases, affected areas of the skin may develop sac-like lesions (vesicles or bullae), scar, and/or become discolored (hyperpigmentation) if exposure to sunlight is prolonged. However, scarring and/or discoloring of the skin is uncommon and rarely severe. These affected areas of skin may become abnormally thick. In addition, in some cases, affected individuals may also exhibit malformations of the nails. The severity and degree of photosensitivity is different from case to case. Photosensitivity is often seen during infancy; however, in some cases, it may not occur until adolescence or adulthood.
In some affected individuals, the flow of bile through the gallbladder and bile ducts (biliary system) may be interrupted (cholestasis) causing gallstones (cholelithiasis) to form. In turn, such stones can cause obstruction and/or inflammation of the gallbladder (cholecystitis). Rarely, affected individuals may also develop liver damage that, in very severe cases, may lead to liver failure requiring transplantation.
Symptoms usually start in childhood but diagnosis is often delayed since blistering is not common and, because the porphyrins are insoluble, they usually escape detection on urinanalysis. The diagnosis is made upon finding increased levels of the protoporphyrin in the plasma or red blood cells.
Erythropoietic protoporphyria is a rare disorder inherited as an autosomal dominant genetic trait with poor penetrance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
The symptoms of erythropoietic protoporphyria develop due to excessive levels of a chemical called protoporphyrin that accumulates in certain tissues of the body (i.e., the plasma, red blood cells, and the liver). Excessive protoporphyrin levels occur as the result of abnormally low levels of the enzyme ferrochelatase (FECH).
There are several different allelic variants of erythropoietic protoporphyria. An allele is any of a series of two or more genes that may occupy the same position (locus) on a specific chromosome. Symptoms of these allelic variants of erythropoietic protoporphyria are predominantly the same; however, one type may be inherited as an autosomal recessive genetic trait.
The gene that is responsible for regulating the production of the enzyme ferrochelatase (FECH) has been located on the long arm of chromosome 18 (18q21.3). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”.
Some people who have inherited this defective gene may have slightly elevated levels of protoporphyrin in the body but will not exhibit the symptoms of erythropoietic protoporphyria.
Affected Populations
Erythropoietic protoporphyria is a very rare inherited disorder that affects males and females in equal numbers. It is estimated that the disorder occurs in about 1 in about 74,300 individuals. The onset of symptoms affecting the skin usually occurs in infancy; however, in some cases, onset may not occur until adolescence or adulthood. More than 300 cases of EPP have been reported in the medical literature.
Related Disorders
Symptoms of the following disorders can be similar to those of EPP. Comparisons may be useful for a differential diagnosis:
There are several other types of porphyrias, all of which involve deficiencies of specific enzymes. Most of the symptoms of these porphyrias are not similar to the symptoms found in erythropoietic protoporphyria. Individuals with porphyria cutanea tarda and congenital erythropoietic porphyria may develop skin lesions; however, these lesions do not resemble the skin lesions found in EPP. It is important to note that individuals with one type of porphyria do not develop any of the other types. In addition, there are skin disorders characterized by hypersensitivity to artificial light and sunlight besides EPP, such as xeroderma pigmentosum and epidermolysis bullosa. The skin lesions in these disorders do not resemble the skin lesions in EPP. (For more information on these disorders, choose “Porphyria and Epidermolysis Bullosa” as your search terms in the Rare Disease Database.)
Xeroderma pigmentosum (XP) is a group of rare inherited skin disorders characterized by hypersensitivity of sunlight and some types of artificial light, with skin blistering occurring after such exposure. In some cases, pain and blistering may occur immediately after contact with sunlight or artificial light. Acute sunburn and persistent redness or inflammation of the skin (erythema) are also early symptoms of xeroderma pigmentosum. In most cases, these symptoms may be apparent immediately after birth or occur within the next three years. Other skin symptoms of xeroderma pigmentosum may include discolorations of the skin, weak and fragile skin, and/or scarring of the skin. Xeroderma pigmentosum also affects the eyes; the most common symptom being an extreme intolerance to light (photophobia). Additional symptoms may include some neurological impairments, short stature, an increased susceptibility to some forms of cancer (e.g., skin cancer). There are several types of xeroderma pigmentosum; in most cases, XP is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Xeroderma Pigmentosum” as your search terms in the Rare Disease Database).
The diagnosis of erythropoietic protoporphyria (EPP) may be made by a thorough clinical evaluation, characteristic physical findings, and specialized laboratory tests. EPP is usually diagnosed during infancy or early childhood, due to characteristic skin symptoms. The diagnosis may be confirmed by testing the red blood cells (erythrocytes) for increased levels of protoporphyrin.
Standard Therapies
Avoidance of sunlight will be of benefit to individuals with erythropoietic protoporphyria. The use of topical sunscreens, double layers of clothing, long sleeves, hats, and sunglasses will also benefit photosensitive individuals. Individuals with EPP may also benefit from window tinting or using vinyls or films to cover the windows in their car or house. Before tinting or shading car windows, affected individuals should check with their local Registry of Motor Vehicles to ensure that such measures do not violate any local codes.
In erythropoietic protoporphyria, a high potency form of oral beta-carotene (Lumitene, Tishcon) may be given to improve an affected individual's tolerance of sunlight. For more information on this treatment, contact the organizations listed at the end of this report (i.e., American Porphyria Foundation and the EPPREF) and Mr. George McShane of the Tishcon Corp. (1-800-848-8442). In some cases, the drug cholestyramine may be given to alleviate skin symptoms and lower the protoporphyrin levels in the body.
When iron deficiency is present, iron supplements may be given. A type of bile acid (chenodeoxycholic acid) may be prescribed to help the liver dispose of excess protoporphyrin, and activated charcoal or cholestyramine may be used to interrupt the circulation of protoporphyrin through the liver and intestines.
Estrogens and drugs that can impair bile flow should be given cautiously under the supervision of a physician. In addition, individuals with high levels of protoporphyrin in the plasma and red blood cells should be observed closely by a physician for possible liver malfunction that could eventually lead to liver failure.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
Investigational Therapies
Information on current clinical trials is posted on the Internet at All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
For information about clinical trials sponsored by private sources, contact:
The orphan product L-Cysteine is being tested for the prevention and reduction of photosensitivity in erythropoietic protoporphyria. More research is needed to determine the long-term safety and effectiveness of this drug for the treatment EPP. For more information, contact:
Micheline M. Mathews-Roth, M.D.
Channing Laboratory
Harvard Medical School
181 Longwood Ave
Boston, MA 02115-5804
Red blood cell transfusions have also been used to treat some people with EPP. In some affected individuals with severe liver disease, liver transplantations have been performed. Extreme caution should be used by physicians considering these treatment options; each particular case should be evaluated on its own merits.