Each disease in the porphyria family results from deficiencies in a specific enzyme involved in the biosynthesis of heme also called the porphyrin pathway. Erythropoietic protoporphyria epp is a rare, inherited disorder of. Vampires may have been real people with erythropoietic. Erythropoietic protoporphyria epp, with a reported prevalence of 1 in 75 000 to 1 in 200 000, 1 is the most common porphyria in children. Erythropoietic protoporphyria epp is a type of porphyria. In about 96% of cases an affected individual inherits a lossoffunction fech allele from one parent and. Erythropoietic protoporphyria epp european porphyria. In most cases, affected individuals have one severe lossoffunction mutation that is inherited from one parent, and another weak lowexpression mutation that is inherited from the other parent. The patterns of inheritance led the researchers to conclude the mutation must come from an enzyme on the xchromosome with alas2 being the most likely candidate. Erythropoietic protoporphyria orphanet journal of rare. Erythropoietic protoporphyria epp is an inherited cutaneous. Narrower 1 protoporphyria, erythropoietic, xlinked dominant.
In most cases, epp is caused by mutations in the ferrochelatase gene. Protoporphyrin is excreted by the liver into the bile. Xlinked dominant erythropoietic protoporphyria is a relatively mild version of porphyria with the predominant symptom being extreme photosensitivity causing severe itching and burning sensation of the skin due to the buildup of protoporphyrin ix. Erythropoietic protoporphyria epp is a porphyria of the erythropoietic class, in which a rare genetic disorder of heme metabolism results in the accumulation of protoporphyrin ix, the lipid soluble, photosensitive precursor of hemoglobin. Erythropoietic protoporphyria and xlinked protoporphyria uptodate. Sep 10, 2009 erythropoietic protoporphyria epp is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. Erythrohepatic protoporphyria definition of erythrohepatic.
Longterm observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Erythropoietic protoporphyria pathology dermnet nz. This is the commonest erythropoietic form of porphyria one in which it is predominantly erythroid haem synthesis which is disturbed. Both sexes are equally affected, the disease does not skip generations and there is frequently a history of the porphyria in other family members. Erythropoietic protoporphyria epp is an inherited disorder of heme biosynthesis that results from an accumulation of protoporphyrin ix in erythroid cells, plasma, skin and liver. How is erythropoietic protoporphyria epp inherited. Erythropoietic protoporhyria in first pregnancy in. Erythropoietic protoporphyria epp european porphyria network. Patients with epp feel a burning sensation in their skin, and experience redness and swelling. Heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. Patients with epp have mutations in one or more genes that cause them to have decreased activity of an enzyme called protoporphyrin ix in their red blood cells.
Epp leads to acute photosensitivity and, in about 2% of patients, liver disease. Erythropoietic protoporphyria definition of erythropoietic. These individuals develop often gall stones later in life. Xlinked protoporphyria nord national organization for. Continuing and persistent burning pain, isolation and a lack of understanding from peers has a long term impact on patients diagnosed with erythropoietic protoporphyria epp. Broader 2 disorders of porphyrin metabolism hereditary diseases. Erythropoietic protoporphyria pathology britannica. Porphyrins are chemicals that are important for manufacturing blood. Erythropoietic protoporphyria epp is characterized by cutaneous photosensitivity usually beginning in infancy or childhood that results in tingling, burning, pain, and itching within minutes of sunlight exposure and may be accompanied by swelling and redness.
Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals. Enzymes that cause both epp and xlpp are in the heme biosynthetic pathway see table substrates and enzymes of the heme biosynthetic pathway. Brief exposure to sunlight can cause severe pain, burning, erythema, and edema of the exposed skin. Introduction to erythropoietic protoporphyria 1 epp1 epp1 is an autosomal recessive disorder that is a member of a family of disorders referred to as the porphyrias. A clinically similar form of porphyria, known as x.
It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the red blood cells erythrocytes, plasma, skin, and liver. Urosynthetase is the fourth enzyme in the heme biosynthesis pathway, and it normally converts hydroxymethylbilane to uroporphyrinogen iii. The gene for human ferrochelatase fech has been mapped to 18q21. Erythropoietic protoporphyria causes, symptoms, diagnosis. Urosynthetase is the fourth enzyme in the heme biosynthesis pathway, and it normally converts hydroxymethylbilane to. Erythropoietic protoporphyria and xlinked protoporphyria are conditions related to deficiencies of enzymes involved in the production of heme and characterized by sensitivity to sunlight.
Erythropoietic protoporphyria epp is a rare inherited metabolic disorder characterized by a deficiency of the enzyme ferrochelatase fech. It differs from the other porphyrias in several respects. Epp and xlp are rare cutaneous porphyrias due to deficiencies of the enzymes ferrochelatase or. Autosomal recessive erythropoietic protoporphyria in the united. Erythropoietic protoporphyria is caused by pathogenic variants mutations in the fech gene which. N erythropoietic protoporphyria epp is an inherited. Dec 18, 2019 the term protoporphyria now encompasses 2 clinically similar but distinct disorders that most often result from hereditary mutations in 2 different genes. Clinical picture of a 14yearold boy with erythopoietic protoporphyria. Recessive inheritance of erythropoietic protoporphyria with. It predominantly affects haem synthesis in red blood cells, rather than other organs such as the liver. In epp there is a buildup of one particular porphyrin called protoporphyrin that is produced in excess from the bone marrow. Erythropoietic protoporphyria epp was first described by magnus and associates in 1961. Congenital erythropoietic porphyria metabolic disorders.
The disorder most often results from inheritance of a null fech allele in trans with a lowexpression fech mutation 612386. Fech, alas2 erythropoietic protoporphyria epp and xlinked protoporphyria xlp are both protoporphyrias with similar symptoms and similar biochemical findings, but each is caused by mutations in a different gene. Epp is normally inherited in an autosomal dominant pattern with low clinical. Symptoms which may seem out of proportion to the visible skin. Other articles where erythropoietic protoporphyria is discussed. Epp is due to an inherited deficiency of the enzyme. Mode of inheritance in erythropoietic protoporphyria epp is complex and can be either autosomal dominant with low clinical penetrance, as is in most cases, or autosomal recessive. Erythropoietic protoporphyria 9 uncommon skin conditions. Erythropoietic protoporphyria and xlinked protoporphyria. Erythropoietic protoporphyria genetic and rare diseases. Erythropoietic protoporphyria porphyria for professionals. The lancet short reports recessive inheritance of erythropoietic protoporphyria with liver failure r. Symptoms which may seem out of proportion to the visible skin lesions may persist for hours or. Erythropoietic protoporphyria porphyria for patients.
Another type of protoporphyria caused by mutations in the deltaaminolevulinic acid synthase2 gene is known as xlinked protoporphyria xlp. Erythropoietic protoporphyria epp is a member of a group of diseases called the porphyrias. In the case of erythropoietic protoporphyria epp and a variant of epp called xlinked dominant protoporphyria xldpp, there is a buildup of one of these porphyrins protoporphyrin in the blood, especially in the red blood cells. While the main symptom is intolerance to sunlight, these patients are at risk for liver. Porphyrias are caused by an abnormality in the heme production process. In contrast to most xlinked disorders, which are recessive, xlinked dominant disorders are evident in a female with one normal x chromosome and one affected x chromosome. The recent development of simple assays for ferrochelatase activity and cloning of the human ferrochelatase gene promises to shed light on the transmission of this disorder and may allow clinical expression of disease. Erythropoietic protoporphyria epp is one of the less common forms of porphyrias. Erythropoietic protoporphyria is inherited in an autosomal recessive manner 98% of cases.
Erythropoietic protoporphyria is caused by pathogenic variants mutations in the fech gene which lead to an impaired activity of ferrocheletase. It presents in infancy when even after a short exposure to sunlight there is a burning pain in the skin. Erythropoietic protoporphyria epp is due to an inherited deficiency in the activity of the enzyme ferrochelatase. Heme is a vital molecule for all of the bodys organs, although it is most abundant in the blood, bone marrow, and liver. Erythropoietic protoporphyria epp is a metabolic condition caused by deficiency of the ferrochelatase enzyme leading to intracellular accumulation of haeme precursors. Nov 14, 2015 erythropoietic protoporphyria epp is a genetic disorder characterized by accumulation of protoporphyrin. Porphyrins are chemicals that are important for manufacturing blood and enzymes within the body. This enzyme belongs to the pathway of heme synthesis and catalyzes the insertion of ferrous iron into the protoporphyrin ix ring to form heme the last reaction of this pathway. Symptoms of erythropoietic protoporphyria including medical symptoms and signs of erythropoietic protoporphyria, alternative diagnoses, misdiagnosis, and correct diagnosis for erythropoietic protoporphyria signs or erythropoietic protoporphyria symptoms. Erythropoietic protoporphyria epp is a form of cutaneous porphyria that manifests mainly as a skin condition. Erythropoietic protoporphyria medical definition merriam. Erythropoietic protoporphyria epp is a genetic disorder characterized by accumulation of protoporphyrin. It has a phenotype very similar to erythropoietic protoporphyria epp, but is distinguished from.
Presentation is with acute photosensitivity in childhood giving rise to erythema and scale and eventually scarring and waxlike thickening of the. A life in the shadow erythropoietic protoporphyria epp. Erythropoietic protoporphyria epp is one of several rare inherited disorders called porphyrias. Inheritance of a mutation on a single allele inherited from either mother or from father is sufficient for the disease to manifest.
Congenital erythropoietic porphyria cep is a rare, hereditary disease of cattle, pigs, cats, and people that results from a significant yet variable decrease in uroporphyrinogen iii synthase urosynthase activity. The cutaneous porphyrias include cep, erythropoietic protoporphyria epp, xlinked protoporphyria xlp, and porphyria cutanea tarda pct. The more common of these is erythropoietic protoporphyria, epp, omim 177000, which is caused by impaired activity of ferrochelatase fech, the ultimate enzyme of heme biosynthesis. Epp is caused by a deficiency of the enzyme, ferrochelatase in the heme biosynthesis pathway, due to mutations in the fech gene. Barry paw of the danafarberboston childrens cancer and blood disorders center, has identified a genetic mutation that may be responsible for. Erythropoietic protoporphyria and xlinked dominant.
Apr 11, 2018 erythropoietic protoporphyria epp is a type of porphyria. A condition where there is excessive formation of porphyrin or its precursor. Xlinked protoporphyria xlpp is due to an inherited increase in the activity of deltaaminolevulinic acid synthase2. One possible treatment was discovered when treating an individual with supplemental iron for a gastric ulcer. Epp has been reported worldwide, with prevalence between 1. Erythropoietic protoporphyria epp is a rare autosomal dominant disorder of heme biosynthesis characterized by partial decrease in ferrochelatase fech. In this condition, the skin is severely sensitive to light, which often presents as scarring, blistering, and hair growth on the handsface.
Xlp have almost the same symptoms as the epp in males, but appears to have a higher risk for liver problems than does epp. Heme is a component of several ironcontaining proteins called hemoproteins, including hemoglobin the protein. Erythropoietic protoporphyria epp is one of a group of genetic diseases called the porphyrias. There are only a few families known to us in south africa carrying this condition. It usually manifests in early infancy upon the first sun exposures. Erythropoietic protoporphyria there are approximately 20 families with erythropoietic protoporphyria in south africa. The severity varies significantly from individual to individual. A novel fech mutation causes erythropoietic protoporphyria with.
Erythropoietic protoporphyria and xlinked protoporphyria nord. Erythropoietic protoporphyria, known as epp, is a disease characterized by extreme sensitivity to light. Prof t m cox department of medicine, university of cambridge, level 5, addenbrookes hospital, cambridge cb2 2qq, uk erythropoietic protoporphyria is characterised by skin photosensitivity and deficiency of. Erythropoietic protoporphyria epp is a rare inherited metabolic disorder caused by a deficiency of the enzyme ferrochelatase fech, which results from changes mutations in the fech gene.
Erythropoietic protoporphyria is caused by pathogenic variants mutations in the fech gene which lead to an impaired. Erythropoietic protoporphyria epp is characterized by cutaneous photosensitivity. Omim online mendelian inheritance in man search term erythropoietic protoporphyria biolcati g, marchesini e, sorge f, barbieri l, schneideryin x, minder ei. Erythropoietic protoporphyria epp is a rare inherited metabolic disorder caused by. Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. The term protoporphyria now encompasses 2 clinically similar but distinct disorders that most often result from hereditary mutations in 2 different genes. The heme precursor protoporphyrin accumulates in the bone marrow, red blood cells, and other tissues, including skin. Erythropoietic protoporphyria, autosomal recessive. Xlinked dominant protoporphyria xldpp was first reported in the genetics literature in 2008. Xlinked protoporphyria is caused by gainoffunction mutations to the alas2 gene located on the x chromosome and is inherited as an xlinked dominant disorder. Erythropoietic protoporphyria epp is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. Patients with epp feel a burning sensation in their skin, and. Epp is normally inherited in an autosomal dominant pattern with low clinical penetrance.
Semantic scholar uses ai to extract papers important to this topic. Heme is a component of several ironcontaining proteins called hemoproteins, including hemoglobin the protein that carries oxygen in the blood. Due to abnormally low levels of this enzyme, excessive amounts of protoporphyrin accumulate in the bone marrow, blood plasma, and red blood cells. Erythropoietic protoporphyria has an indeterminate pattern of inheritance and may be complicated by fulminating liver disease. Medical definition of erythropoietic protoporphyria. Erythropoietic protoporphyria an overview sciencedirect. More detailed information about the symptoms, causes, and treatments of erythropoietic protoporphyria is available below symptoms of erythropoietic protoporphyria. In epp there is a buildup of one particular porphyrin called protoporphyrin that. Symptom severity in erythropoietic protoporphyria and xlinked protoporphyria varies greatly, even among patients within a single family. Erythropoietic protoporphyria is a form of porphyria, which varies in severity and can be very painful. Erythropoietic protoporphyria epp is an uncommon inherited porphyria, first identified in the early 1960s, that affects about 1150 000 of the population in western europe. The transmission pattern of erythropoietic porphyria in the families reported by whatley et al. Anemia, hemolytic autosomal recessive inheritance biliary calculi burning sensation. Presentation is with acute photosensitivity in childhood giving rise to erythema and scale and eventually scarring and waxlike thickening of the skin histology of erythropoietic protoporphyria.
Treatments for erythropoietic protoporphyria including drugs, prescription medications, alternative treatments, surgery, and lifestyle changes. The diagnosis and management of erythropoietic protoporphyria. Sep 27, 2012 erythropoietic protoporphyria epp is characterized by cutaneous photosensitivity usually beginning in infancy or childhood that results in tingling, burning, pain, and itching within minutes of sunlight exposure and may be accompanied by swelling and redness. It usually manifests in early infancy upon the first sun. Mode of inheritance in erythropoietic protoporphyria epp is complex and can be either autosomal dominant with low clinical penetrance, as is in most cases. Erythropoietic protoporphyria epp is a blood disorder due to a hereditary enzyme defect in the heme synthesis of the red blood cell.