Friday, May 19, 2017

NIH Updated Info on the Porphyrias 3/22/17

 https://rarediseases.info.nih.gov/diseases/10353/porphyria

Porphyrias are a group of blood conditions caused by a lack of an enzyme in the body that makes heme, an important molecule that carries oxygen throughout the body and is vital for all of the body’s organs. Major types include ALAD deficiency porphyria, acute intermittent porphyria, congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, hereditary coproporphyria, porphyria cutanea tarda, and variegate porphyria. The most common type of porphyria is porphyria cutanea tarda. Some of the symptoms of porphyria include blistering, swelling, and itching when the skin is exposed to sun. Other symptoms may also include pain, numbness or tingling, vomiting, constipation, and intellectual disability. There is no known cure for porphyria, but the various types have different courses of treatment, and may include bone marrow transplant.[1]

Most porphyrias are inherited conditions with either an autosomal dominant or autosomal recessive pattern of inheritance. However, some forms of porphyria can be caused by environmental factors such as infections or exposures to certain prescription drugs. Porphyrias caused by environmental factors are called sporadic or acquired porphyria.[2][3]
Last updated: 3/22/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.
Signs and SymptomsApproximate number of patients (when available)Help
Abnormal urinary colorVery frequent
(present in 80%-99% of cases)
Abnormality of the heme biosynthetic pathwayVery frequent
(present in 80%-99% of cases)
Abdominal painFrequent
(present in 30%-79% of cases)
Abnormal blistering of the skinFrequent
(present in 30%-79% of cases)
Abnormality of skin pigmentationFrequent
(present in 30%-79% of cases)
AnorexiaFrequent
(present in 30%-79% of cases)
Chest painFrequent
(present in 30%-79% of cases)
ConstipationFrequent
(present in 30%-79% of cases)
Cutaneous photosensitivityFrequent
(present in 30%-79% of cases)
DiarrheaFrequent
(present in 30%-79% of cases)
FatigueFrequent
(present in 30%-79% of cases)
HypertensionFrequent
(present in 30%-79% of cases)
Nausea and vomitingFrequent
(present in 30%-79% of cases)
PruritusFrequent
(present in 30%-79% of cases)
Sleep disturbanceFrequent
(present in 30%-79% of cases)
Cerebral palsyOccasional
(present in 5%-29% of cases)
Dupuytren contractureOccasional
(present in 5%-29% of cases)
FeverOccasional
(present in 5%-29% of cases)
HallucinationsOccasional
(present in 5%-29% of cases)
ParesthesiaOccasional
(present in 5%-29% of cases)
SeizuresOccasional
(present in 5%-29% of cases)

Last updated: 3/10/2017

Many of the signs and symptoms of porphyria are similar to those of other more common diseases. Also, because porphyria is rare, many doctors have not seen cases of the disorder before, making it more difficult to diagnosis. Because porphyria's signs and symptoms usually aren't distinctive, laboratory tests are required to make a definitive diagnosis and to determine which type of porphyria is involved.[4] If your doctor suspects porphyria, he or she may recommend the following tests:[4][5]
  • Urine test. If you have a form of acute porphyria, a urine test may reveal elevated levels of two substances: porphobilinogen and delta-aminolevulinic acids, as well as other porphyrins.
  • Blood test. If you have a form of cutaneous porphyria, a blood test may show an elevation in the level of porphyrins in the liquid part of your blood (plasma).
  • Stool sample test. Analysis of a stool sample may reveal elevated levels of some porphyrins that may not be detected in urine samples. This test may help your doctor determine your specific type of porphyria.
Genetic testing may also be used to confirm the diagnosis.[5]
Last updated: 11/4/2016

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.  

    Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

    Clinical Research Resources

    • ClinicalTrials.gov lists trials that are studying or have studied Porphyria. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

      Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
    • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

      Patient Registry

      • The Porphyrias Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Porphyrias Consortium has a registry for patients who wish to be contacted about clinical research opportunities.

        For more information on the registry see: http://rarediseasesnetwork.epi.usf.edu/registry/index.htm

        Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

        Organizations Supporting this Disease

          Social Networking Websites

          • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

            Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

            Financial Resources

            • The HealthWell Foundation provides financial assistance for underinsured patients living with chronic and life-altering conditions. They offer help with drug copayments, deductibles, and health insurance premiums for patients with specific diseases. The disease fund status can change over time, so you may need to check back if funds are not currently available.

              These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

              Where to Start

              • Genetics Home Reference (GHR) contains information on Porphyria. This website is maintained by the National Library of Medicine.
              • MayoClinic.com provides information about porphyria. Click on the link to access this information.
              • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
              • The National Digestive Diseases Information Clearinghouse (NDDIC), part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), offers information on this condition. Click on the link to view information on this topic.
              • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
              • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

                In-Depth Information

                • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
                • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
                • The Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
                • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
                • PubMed is a searchable database of medical literature and lists journal articles that discuss Porphyria. Click on the link to view a sample search on this topic.


                  Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question
                  • I would like to be tested for porphyria. How is this condition diagnosed? Is genetic testing available? See answer
                  • What can you tell me about acute intermittent porphyria and Chester porphyria? See answer


                  1. Porphyria. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). February 26, 2014; http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/porphyria/Pages/facts.aspx. Accessed 5/26/2015.
                  2. Porphyria. MedlinePlus. September 24, 2014; http://www.nlm.nih.gov/medlineplus/porphyria.html. Accessed 5/26/2015.
                  3. Porphyria. Genetics Home Reference. July 2009; http://ghr.nlm.nih.gov/condition=porphyria. Accessed 5/26/2015.
                  4. Porphyria. MayoClinic.com. May 20, 2014; http://www.mayoclinic.com/health/porphyria/DS00955/METHOD=print. Accessed 11/4/2016.
                  5. Tests for Porphyria diagnosis. American Porphyria Foundation. http://www.porphyriafoundation.com/testing-and-treatment/testing-for-porphyria/tests-for-porphyria-diagnosis. Accessed 11/4/2016.
                                                               "Remember....Research is your Key to a cure"

                  Friday, May 12, 2017

                  Continue Raising Awareness Year Round

                  THANK YOU!
                  Continue Raising Awareness Year Round
                  We, at the American Porphyria Foundation, would like to THANK YOU for participating in National Porphyria Awareness Week. We are very grateful for everyone who submitted their photos and notified us of their awareness activities. If you are still interested in continuing to RAISE PORPHYRIA AWARENESS,contact the APF.
                  If you have not shared your photos with the APF, please do so, we would love  to see them. Don't stop now! Continue to RAISE PORPHYRIA AWARENESS!
                   
                  The challenge of living with porphyria starts with how little is known about it among friends, family and the medical community.   Here are some suggestions for ways that you can help:
                  *SHARE knowledge about porphyria at your doctor's offices and local hospitals.  You might suggest that they host a seminar or grand rounds on porphyria; ask if there is a local meeting where you can hand out materials.
                  *ASSIST at medical conventions or health fairs to educate family, friends, and physicians on porphyria.
                  *Tell your story to local media. Television, newspapers and community magazines are looking for human interest stories about people who have encountered a major illness and have undertaken the challenge.
                  *VOLUNTEER your talents or skills to help achieve the educational programs of the APF.  For example, donate one of your paintings, sculpture, computer expertise, business acumen etc. for our fall raffle or to help APF.
                  *HOLD a community race, car wash or other fund raising activity.
                  *HONOR your loved one with a gift to the APF for a birthday, anniversary, holiday or memorial tribute.
                  *WRITE a letter to friends and family asking them to consider making a donation;
                  The APF can help you accomplish this goal by providing materials:
                  ·        Porphyria Brochures
                  ·        A Porphyria Live DVD
                  ·        Fact sheets
                  ·        A PowerPoint Presentation
                  ·        Information for Grand Rounds
                  ·        Ideas to set up Medical Seminars
                  ·        Ideas to exhibit at a Health Fair
                  ·        Information to gain press
                  ·        Doctor packets sent to your doctors
                  ·        Press Releases
                  Contact the APF TODAY for more information at 1.866.APF.3635!

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


                  Tuesday, May 9, 2017

                  Darnisha Davenport's Experience with EPP

                  After many years, I'm finally comfortable with being open about my health condition. This is one of the reasons that pushed me to start iKURLY. Not just for my hair, but it copes with my disorder as well. I have been living with a rare skin disorder since I was 15 years old. After so many doctor visits, dermatology consultations, and skin creams prescribed, no one could help me, not even knowing what it was. None of those things worked, just created medical bills out the roof. I stayed humble and did whatever I thought was needed to avoid the reactions, but as I get older, it's only getting worse. Recently I was diagnosed with EPP, short for Erythropoietic Protoporphyria. It is a rare skin disorder. It is not fun. It is painful, very painful and it burns. When I have outbreaks I can't do anything but step in shade, apply ice and become isolated so I can calm down. People use to make fun of me laughing at the fact me being allergic to the sun, but it's actually deeper than that. As life goes on I try to remain positive, happy because deep down inside I know I am blessed, and even though this makes me different...every day I try to look at it as a positive, that this is just one more way God added to my uniqueness from others. It kills me sometimes though, because as a little girl all my family did was TRAVEL...down South, sunny states you name it, and now when I try to go somewhere on vacation or just everyday living, I have to be cautious and stay protected. Pictured was my recent reaction. This is just a glimpse of what it looks like. My face swelled, I turn completely red, my skin was on fire..it's an excruciating pain you just have to endure until it goes away. I go through my moments. This is things people don't see or hear, I stay strong because I am strong to beat this.  The tears shed, people don't know what you go through daily, they judge your strength and how you wear it. I thank God I don't look like what I've been through. Even with my disorder my goal is to continue spreading happiness and positivity. I am now a part of a Foundation that is assisting me with specialist in finding a cure, and next week I'll be starting treatments. This is my testimony. Pray for me.
                  To learn more about EPP or sign up for Research opportunities please click on these links:
                  https://www.rarediseasesnetwork.org/cms/porphyrias
                  http://www.porphyriafoundation.com/get-involved/join-the-registry
                                       Contact the APF TODAY for more information at 1.866.APF.3635!

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




                  Friday, May 5, 2017

                  The Diagnosis and Management of Erythropoietic Protoporphyria

                  The Diagnosis and Management of Erythropoietic Protoporphyria
                  This article has been cited by other articles in PMC.
                  Abstract
                  Porphyrias are a group of metabolic disorders resulting from enzymatic defects in the heme biosynthetic pathway. Erythropoietic protoporphyria is thought to be the second most common porphyria seen in clinical practice. It is, however, commonly under-recognized and can lead to both cutaneous manifestations as well as derangement in hepatic function in a minority of patients. This review summarizes the current understanding of this disorder. Different treatment options are discussed with the goal of preventing liver damage. The roles of liver and bone marrow transplantation are also addressed.
                  Keywords: Erythropoietic protoporphyria, metabolic disorders
                  Porphyrias are a group of metabolic disorders caused by defects in the heme biosynthetic pathway. Heme is the critical prosthetic group for numerous hemoproteins such as hemoglobin, myoglobin, catalase, and microsomal cytochromes. The term “porphyria” is derived from the Greek word “porphyra,” which means “purple.” The biochemical hallmark of porphyrias is overproduction and, ultimately, overexcretion of compounds called porphyrins, which have a deep red or purple color. The first clinical reports of porphyria appeared in the late nineteenth century and described a patient with severe cutaneous photosensitivity and brown pigmentation of the bones, which is characteristic of congenital erythropoietic porphyria. Soon thereafter, a case of acute porphyria was described in a person addicted to drugs who had urine the color of port wine and later died after taking the hypnotic drug sulfonomethane.
                  Porphyrias can present clinically either with neurovisceral symptoms and signs such as abdominal pain, constipation, and weakness or with cutaneous symptoms and signs. In hereditary coproporphyria and variegate porphyria, patients may present with both types of symptoms; in the other forms of porphyria, patients manifest only one type of clinical presentation. When considering therapy for porphyrias, it is useful to classify the disorders into two major categories: acute/inducible porphyrias or chronic cutaneous porphyrias (Table 1). Regardless of the specific type of acute porphyria or associated enzymatic defect, all of the acute porphyrias produce similar neurovisceral manifestations and should be managed in a similar manner. Management of cutaneous porphyria, though more specific to the particular type of porphyria, also involves the application of several general principles.
                  Table 1
                  Classification and Major Features of Human Porphyrias
                  Enzymatic Defects and Genetics
                  Erythropoietic protoporphyria (EPP) was first described by Magnus and associates in 1961.1 Bonkovsky and colleagues demonstrated that heme synthase or ferrochelatase (FECH), an inner mitochondrial enzyme, was deficient in this disorder (Figure 1).2 Since then, the gene for FECH has been localized to 18q21,3,4and approximately 120 disease-producing mutations have been described to date. The gene has 11 exons and a minimum size of 45 kb. From early studies of kindreds with EPP, most investigators concluded that the disease displayed autosomal dominant inheritance with low penetrance and an increased propensity to develop chronic liver disease,5 though autosomal recessive forms of EPP have also been described.6 The activity of ferrochelatase in clinically affected patients is approximately 15–25% of normal activity. The parents of many patients are asymptomatic and phenotypically normal, though approximately one half demonstrate decreases in ferrochelatase activity. More recent familial studies have identified a single nucleotide polymorphism (IVS3-48C), which leads to a lower level of expression of the normal FECH gene allele.7 Patients develop clinical disease with less than 25% of normal FECH activity when a mutated allele is inherited along with the low-level-expressing, wild-type allele, which usually harbors the IVS3-48C polymorphism. One recent paper stressed the importance of large deletions in the FECH gene exons as an important cause of “mutation-negative” EPP.8
                  Figure 1
                  The heme biosynthetic pathway.
                  FECH carries out the ultimate step in heme biosynthesis, namely the insertion of ferrous iron into protoporphyrin for the formation of heme. The only difference between heme and protoporphyrin is the insertion of an iron atom into the tetrapyrrole ring in heme. This insertion increases the stability of the structure and results in the loss of its fluorescent properties. In EPP, the major site of protoporphyrin overproduction is localized to the bone marrow, where erythrocytes are developed.912 Protoporphyrin, unlike other porphyrins, is water-insoluble and therefore removed from the body only through hepatic excretion into bile or feces. Protoporphyrin is not excreted in urine, though it does undergo some enterohepatic circulation.
                  Epidemiology and Clinical Presentation
                  Of all the porphyrias found in the United States, EPP is thought to be second in prevalence only to porphyria cutanea tarda. The exact prevalence of EPP has not been reliably estimated due to its frequently mild nature and normal urinary porphyrins, which increase the possibility of missing bona fide cases. There is no gender predominance in EPP, which is found across all ethnic and racial groups.
                  EPP, a disorder with highly variable clinical expression, has been previously well characterized as a chronic cutaneous porphyria.1316 Most affected patients present in early childhood with sun sensitivity and, at times, an urticarial-type reaction. Infants and children classically develop intense burning pain from sun-exposed skin following brief exposure in the spring and summer. Several hours later, erythema, edema, and itching become prominent. Vesicles are uncommon and develop only with prolonged sun exposure. With chronic and repeated exposure, involved skin may become leathery and hyperkeratotic. This reaction is particularly prominent in a malar “butterfly” pattern on the face and over the knuckles of the hands. Patients usually have a chronic and stable disease course, with no identified aggravating factors.
                  Photoactivation of lipid-soluble protoporphyrin, which is deposited in the dermal blood vessels, leads to the characteristic skin burning from sun exposure. Chronic facial scarring, hirsutism, and fluorescent teeth, which are common in congenital erythropoietic porphyria or hepatoerythropoietic porphyria, are not usually found in EPP.16 Photoactivation of circulating water-soluble uroporphyrins, on the other hand, leads to chronic blistering, as seen in congenital erythropoietic porphyria and porphyria cutanea tarda.
                  The most serious complication of EPP is development of pigmentary cirrhosis of the liver.17,18 Fortunately, liver injury is evident in only a minority of patients with EPP (-10%), with approximately 3–5% of the patients eventually developing end-stage liver disease. The pattern of liver injury, when seen in this disorder, typically develops over a period of time and ranges from mild liver disease with elevations in liver enzymes to progressive liver disease with extensive bridging fibrosis or cirrhosis and other concomitant complications. By itself, EPP rarely presents as true acute liver injury, though there may be sudden acute worsening of underlying chronic liver disease.19 Liver disease is thought to develop due to the precipitation of protoporphyrin in hepatocytes and biliary radicles.20,21 No risk factors have been identified that are able to predict the development of liver disease in EPP thus far.
                  A common complication of EPP is the development of pigment gallstones, which have a high content of protoporphyrin. In bile, protoporphyrin may crystallize, providing the nidus for development of gallstones. When evident in children, gallstones should prompt evaluation for EPP.22 Mild anemia with or without hemolysis is occasionally noted. In EPP, abdominal pain and neuropathy-like symptoms are seen only rarely and in the setting of advanced liver disease.2326 Of note, motor neuropathy can develop both pre- and postoperatively at the time of liver transplantation.
                  Diagnosis
                  The diagnosis of EPP requires the demonstration of increased levels of protoporphyrin, without increased levels of coproporphyrin, in the stool, RBCs, or both.27 In EPP, elevated levels of erythrocyte protoporphyrin, plasma protoporphyrin, and stool protoporphyrin are evident. Urinary porphyrin levels are usually normal because, as already mentioned, protoporphyrin is not excreted into the urine. Analysis of the plasma porphyrin emission spectrum reveals a characteristic peak at approximately 634–636 nm, following excitation with light in the Soret band (-400 nm). Erythrocyte protoporphyrin elevations are also evident in severe iron deficiency and lead poisoning. In EPP, the protoporphyrin is primarily free protoporphyrin, in contrast to iron and lead toxicity, in which predominantly Zn-protoporphyrin is found.28In EPP patients, rising plasma protoporphyrin levels, along with severe elevations in RBC protoporphyrin levels, may portend impending liver failure.29,30 Patients with EPP who develop significant liver disease have been shown to have significant increases in urinary coproporphyrin levels. An inversion of the physiological urinary coproporphyrin isomer III/I ratio has also been observed in patients with protoporphyria who develop cholestatic cirrhosis.31 Liver biopsy is performed to assess the severity of suspected liver disease, particularly in patients with very high RBC (>5,000 µg/dL) or plasma protoporphyrin (>1,000 µg/dL) concentrations. Polarized microscopy of the biopsy may demonstrate birefringent crystal deposits with characteristic Maltese cross patterns in EPP. Plugging of biliary canaliculi with protoporphyrin may also be evident in patients with advanced liver disease.32
                  Management
                  A multitude of treatment options are available for EPP,27 ranging from efforts to reduce protoporphyrin overproduction in the bone marrow to augmenting its excretion into bile (Table 2). Other agents are used for their cytoprotective properties in conjunction with measures to reduce the circulating pool of protoporphyrin and, on occasion, liver transplantation to correct end-organ damage. Cutaneous protection with opaque sunscreens and barrier clothing cannot be overemphasized. Standard sunscreens are not useful; the only topical sunscreens that are effective at blocking wavelengths greater than 400 nm, with a high sun protection factor (>30), are light-opaque, contain zinc oxide or titanium dioxide, and may be cosmetically unacceptable to some patients. Oral beta-carotene (Solatene, Roche; 60—180 mg orally per day) reduces photosensitivity in approximately 80% of patients over a 1—3 month period after initiation of therapy. Beta-carotene causes yellow-orange discoloration of the skin, and topical beta-carotene cream is ineffective. Beta-carotene is thought to scavenge the free radicals generated by the excitation of protoporphyrin and is dosed to maintain a therapeutic serum level of 600–800 pg/dL.33 Beta-carotene's efficacy has been questioned in the recent literature, and many patients have found their resulting yellow skin difficult to accept. Oral cysteine has also been used and is thought to have a similar mechanism of action.34 Bile-acid binding agents such as cholestyramine35,36 have been used to decrease the enterohepatic circulation of protoporphyrin. Patients have attempted to use long-term activated charcoal as a safe and cheap alternative in the hopes of decreasing intestinal reabsorption of protoporphyrin.37 Intravenous vitamin E was reported in a case report as being effective for reversing liver disease.38 Ursodeoxycholic acid has been used in patients with early liver disease,31 not only because of its ability to enhance the biliary excretion of protoporphyrin, but also because of its cytoprotective properties.3941 However, a recent study in an autosomal recessive mouse model of EPP demonstrated no benefit with the use of ursodeoxycholic acid and heme arginate.42 Patients are advised against caloric restriction and should undergo iron replacement only if they are found to be iron-deficient.4347
                  Table 2
                  Targets for Intervention
                  Chronic therapy with intravenous hematin and erythrocyte transfusions is thought to suppress heme production4851 by decreasing protoporphyrin levels. Exchange transfusions and plasmapheresis have been used to remove the protoporphyrin in transit, as a bridge to liver transplantation or other more definitive treatments. Heme therapy, along with plasmapheresis, has been noted to stabilize patients with advanced liver disease.5254 Nonbiologic liver assist devices have been used recently in an attempt to decrease the morbidity associated with motor neuropathy, both in the pre- and postoperative period.55
                  Since the first liver transplantation for EPP-related liver disease in 1980, EPP patients with progressive liver disease have been transplanted with acceptable outcomes. Liver transplant recipients from US centers have been shown to have 1-, 5-, and 10-year survival rates of 85%, 69%, and 47%, respectively.56 These survival rates are similar to those for liver transplants performed for other indications. However, recurrent EPP was found in 65% (11/17) of patients who survived more than 2 months post-transplant. The high incidence of recurrent disease post-transplant is not surprising, as the transplant itself does not correct the primary cause and major source of protoporphyrin overproduction, which has been shown to be in the bone marrow.57 Of all the porphyrias, EPP has the best established indication for liver transplantation as a therapeutic option.58 The previous medical literature, as well as more recent reports, have demonstrated a benefit in EPP patients who receive a bone marrow transplant.59,60 Successful bone marrow transplantation with or without liver transplantation, depending upon the severity of the liver disease, is considered the definitive treatment for EPP.
                  Patients with EPP are at increased risk of developing chronic liver disease and should be vaccinated for hepatitis A and B (and possibly hepatitis E in the near future) in case they are found not to be immune. They should be counseled to avoid hepatotoxins such as alcohol because of the risk of accelerating their liver disease.61 EPP patients with no evident liver disease should be monitored with liver enzymes and porphyrin levels, both serum and RBC protoporphyrin, at least every 6 months, if not more frequently, to detect early signs of liver injury.62 Patients with known chronic liver disease should also be screened regularly for hepatocellular carcinoma.
                  Effective management of EPP involves the judicious use of all available treatment options to prevent disease progression and possibly achieve cure. Treatment is directed at minimizing complications from sun damage, monitoring for development of liver disease, and stabilizing cholestatic liver disease once it develops, in the hopes of a more definitive treatment such as bone marrow transplantation with or without liver transplantation. The initial experience with bone marrow transplantation is promising, though the opportune moment to intervene remains unclear.
                  References
                  1. Magnus IA, Jarrett A, Prankerd TA, Rimington C. Erythropoietic protoporphyria. A new porphyria syndrome with solar urticaria due to protoporphyrinaemia. Lancet. 1961;2:448–451. [PubMed]
                  2. Bonkovsky HL, Bloomer JR, Ebert PS, Mahoney MJ. Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts. J Clin Invest. 1975;56:1139–1148. [PMC free article] [PubMed]
                  3. Taketani S, Inazawa J, Nakahashi Y, Abe T, Tokunaga R. Structure of the human ferrochelatase gene. Exon/intron gene organization and location of the gene to chromosome 18. EurJ Biochem. 1992;205:217–222. [PubMed]
                  4. Whitcombe DM, Carter NP, Albertson DG, Smith SJ, Rhodes DA, Cox TM. Assignment of the human ferrochelatase gene (FECH) and a locus for protoporphyria to chromosome 18q22. Genomics. 1991;11:1152–1154. [PubMed]
                  5. Sarkany RP, Alexander GJ, Cox TM. Recessive inheritance of erythropoietic protoporphyria with liver failure. Lancet. 1994;343:1394–1396. [PubMed]
                  6. Gouya L, Martin-Schmitt C, Robreau AM, Austerlitz F, Da Silva V, et al. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. Am J Hum Genet. 2006;78:2–14. [PMC free article] [PubMed]
                  7. Gouya L, Puy H, Robreau AM, Bourgeois M, Lamoril J, et al. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet. 2002;30:27–28.[PubMed]
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                  NIH Updated Info on the Porphyrias 3/22/17

                    https://rarediseases.info.nih.gov/diseases/10353/porphyria Porphyrias are a group of blood conditions caused by a lack of an  en...