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Erythropoietic Porphyria


Erythropoietic porphyria (EP), or congenital erythropoietic porphyria (CEP), results from a deficiency of an enzyme in the pathway for heme synthesis. This leads to the accumulation of toxic porphyrins, which make tissues photosensitive. The major manifestations are blistering skin conditions, often severe and leading to deformities, and hemolytic anemia. Allogeneic bone marrow transplantation is curative.


Erythropoietic porphyria (EP) belongs to the porphyria group of disorders. These arise from deficiencies in enzymes that catalyze steps in heme biosynthesis. Manifestations of the disease vary and depend on the metabolic intermediates that accumulate and the organs primarily affected. Based on the main organ involved, the porphyria diseases are classified into hepatic and erythroid groups [1].

EP is a very rare disease that arises because of a deficiency of uroporphyrinogen III synthase. This results in spontaneous formation of type I isomers (uroporphyrinogen I and uroporphyrin I); these are dead-end products, which accumulate mainly in red blood cells, plasma, and bone, and are excreted in urine and feces. Porphyrins are colored, fluoresce in UV light, and cause photosensitivity in biomolecules and damage to tissues.

EP is inherited as an autosomal recessive disorder. Manifestations range from severe cases, detected first as jaundice and pink diaper rash in newborns, or even earlier as intrauterine hydrops due to hemolytic anemia, to milder manifestations in adults.

A characteristic feature of the disease is damage, often severe, to the skin, especially in areas exposed to light (face, hands). There are bullous lesions, which rupture easily and become infected. Repeated damage and infections cause scarring, pigmentation, and thickening of the skin. Epidermal atrophy and destruction of cartilage lead to contractures, loss of digits, and deformities on the face and hands [2]. Hypertrichosis of the face is also common. Damage to the eye [3] may occur because of several reasons, among which are inflammation and lagophthalmos; scarring of the cornea may lead to visual loss or even blindness. The teeth can have a red color because of deposition of porphyrin in them. Porphyrins can also collect in the bones and cause bone loss and deformities.

Hemolysis, which occurs to varying degrees, is probably because the deposition of uroporphyrin I in erythrocytes renders them fragile. This effect leads to hemolytic anemia, splenomegaly, and thrombocytopenia. Compensatory bone marrow expansion can result in fragile bones [4].

  • This disease is characterized by splenomegaly; anemia; photosensitivity; cutaneous lesions; accumulation of hydroxymethylbilane; and increased excretion of uroporphyrins and coproporphyrins.[icd10data.com]
  • Patients may display signs and symptoms of anemia usually hemolytic with splenomegaly and porphyrin rich gallstones.[tmg.org.rs]
  • Congenital Erythropoietic Porphyria definition Rare autosomal recessive syndrome characterized by severe mutilating photosensitivity, haemolytic anaemia with splenomegaly, and a decreased life expectancy.[dermis.net]
  • He had a hemolytic anemia with reduced osmotic fragility and splenomegaly with acro-osteolysis.[e-ijd.org]
  • Hemolytic anemia with splenomegaly, acro-osteolysis and retarded growth may be present. [1] - [3] We are reporting a patient of congenital erythropoetic porphyria with hemolytic anemia in a Kashmiri boy.[e-ijd.org]
  • Significant splenomegaly can appear, linked with hemolytic anemia. Bone involvement is constant, with rarefaction of bony architecture and a risk of multiple fractures.[orpha.net]
  • Previously known mutations in the ALAS2 resulted in a loss-of-function mutation causing X-linked sideroblastic anemia.[en.wikipedia.org]
  • Manifestations of porphyria include gastrointestinal, neurologic, and psychologic symptoms, cutaneous photosensitivity, pigmentation of the face (and later of the bones), and anemia with enlargement of the spleen.[medical-dictionary.thefreedictionary.com]
Short Stature
  • stature Decreased body height Small stature [ more ] 0004322 Vertebral compression fractures Compression fracture 0002953 Showing of 39 Last updated: 8/7/2018 The resources below provide information about treatment options for this condition.[rarediseases.info.nih.gov]
  • Additional symptoms may include some neurological impairments, short stature, an increased susceptibility to some forms of cancer (e.g., skin cancer).[porphyriafoundation.com]
Foot Deformity
  • deformities Foot deformity [ more ] 0001760 Abnormality of the hand Abnormal hands Hand anomalies Hand deformities [ more ] 0001155 Abnormality of the heme biosynthetic pathway 0010472 Atypical scarring of skin Atypical scarring 0000987 Cutaneous photosensitivity[rarediseases.info.nih.gov]
  • Clinical features include photosensitive blistering and severe anemia. Wood's lamp fluorescence of the diaper is a useful screening test. We describe a severely affected neonate with systemic involvement due to a homozygous mutation.[experts.umn.edu]
  • Manifestations of porphyria include gastrointestinal, neurologic, and psychologic symptoms, cutaneous photosensitivity, pigmentation of the face (and later of the bones), and anemia with enlargement of the spleen.[medical-dictionary.thefreedictionary.com]
  • They should avoid iron supplementation (unless severely iron deficient ), as iron can increase photosensitivity in EPP. Colestyramine reduces hepatic protoporphyrin content but does not reduce photosensitivity.[dermnetnz.org]
  • It results in cutaneous photosensitivity leading to blistering and scarring of the exposed skin areas.[icd10data.com]
  • Clinical features include photosensitive blistering and severe anemia. Wood's lamp fluorescence of the diaper is a useful screening test. We describe a severely affected neonate with systemic involvement due to a homozygous mutation.[experts.umn.edu]
  • Due to repeated blistering and rupture, the skin becomes thickened, scarred and calcified resembling features of scleroderma.[themedicalbiochemistrypage.org]
  • CEP and HEP occur in childhood with severe blistering skin lesions. PCT occurs in adulthood generally and less severe blistering skin lesions after sun exposure.[rarediseasesnetwork.org]
  • A fifteen year old boy, product of a consanguineus marriage, fifth in the birth order with normal siblings, presented to us with a history of blisters over face,hands and feet on exposure to sunlight since the age of one and a half years.[e-ijd.org]
Skin Lesion
  • However, individuals with porphyria cutanea tarda may develop skin lesions, and these lesions resemble the skin lesions found in CEP.[porphyriafoundation.com]
  • HEP skin lesions.) Figure 2 HEP skin lesions. (From Puy H, Gouya L, Deyback J-C. Porphyrias. Lancet 2010;375:924-37.)[clinicaladvisor.com]
  • The tissue deposition of these compounds causes light-sensitization and CEP is characterized by blistering skin lesions on sun-exposed areas of the skin resulting in severe damage to skin beginning in childhood.[themedicalbiochemistrypage.org]
  • Skin lesions include erythema and bullae that occur on exposure to sunlight. Fragile, poorly healing skin with pruritus, hyperpigmentation and hypertrichosis are other features.[patient.info]
Cutaneous Manifestation
  • Biochemical and molecular studies were undertaken to investigate the nature of the unusually mild phenotype in a 15-year-old boy with only cutaneous manifestations.[jamanetwork.com]
  • The cutaneous manifestations are similar to those in PCT. They can be the only clinical features of these mixed porphyrias.[patient.info]
  • manifestations, notably extreme mechanical fragility of the skin, particularly areas exposed to the sunlight, and by episodes of abdominal pain and neuropathy.[medical-dictionary.thefreedictionary.com]
  • The most effective initial therapy is the avoidance of sun exposure and/or strong light of 400 to 410 nm wavelengths (Soret band) to prevent cutaneous manifestations.[clinicaladvisor.com]
Increased Hair Growth
  • Increased hair growth (hypertrichosis) on sun-exposed skin, brownish-colored teeth (erythrodontia), and reddish-colored urine are common. There may be bone fragility due to expansion of the bone marrow and vitamin deficiencies, especially vitamin D.[sema4.com]
  • The most commonly affected areas include the back of the: Hands Forearms Face Ears Neck The symptoms include: Blisters Itching Swelling of the skin Pain Increased hair growth Darkening and thickening of the skin Causes of Porphyria Each type of porphyria[webmd.com]
  • In more severe cases, other symptoms can include a low level of red blood cells (anemia), enlargement of the spleen, and increased hair growth (hypertrichosis).[porphyriafoundation.com]
  • Increased hair growth (hypertrichosis) on sun-exposed skin, and reddish-colored urine are common.[rarediseasesnetwork.org]
  • Blistering and skin ulcers along with increase hair growth and pigmentation can follow chronic sun exposure.[albertaporphyriasociety.weebly.com]
Red Urine
  • A Diagnosis CEP is suspected in individuals (usually newborns) that show the common symptoms Confirmed by measuring porphyrin levels in the individual's blood A blood sample can also be taken to check for genetic mutations Symptoms Red urine in newborns[prezi.com]
  • Frieden Pediatric Dermatology. 2011; : no 4 Red urine and photosensitive skin rash: Not only was our patientæs urine red, but his teeth had a reddish hue, as well. Ghosh, S.K., Bandyopadhyay, D., Haldar, S., Usatine, R.P.[ijdvl.com]
  • They had recurrent skin bullae, scarring on the face and hands, hirsutism, discoloured fluorescent teeth, red urine, increased haemolysis and grossly increased excretion of porphyrin.[link.springer.com]
  • Red urine is usually the first sign noticed in newborn babies with CEP. The intensity of the redness can vary from day to day.[britishskinfoundation.org.uk]
  • Autosomal recessive porphyria characterized by splenomegaly, photosensitivity, hemolytic anemia, and the appearance of red urine in early infancy; results from increased synthesis of uroporphyrinogen i relative to uroporphyrinogen iii in bone marrow normoblasts[icd10data.com]


Children or adults with skin blistering conditions should be tested for EP. Urinary excretion of porphyrins is increased excessively (100-1000 fold) in EP with about 90% being made up of type I isomers [5]. Concentrations of precursors (for example porphobilinogen) are unchanged. Large amounts of porphyrins (mainly coproporphyrins) also appear in the feces. Red blood cells and plasma also contain increased concentrations of porphyrins. Patients with the highest levels of porphyrins are most affected [5].

Both direct and coupled assays for uroporphyrinogen III synthase activity have been developed [6]. Prenatal diagnosis can be performed by measuring uroporphyrinogen III synthase enzyme activity in chorionic villi or cultured amniotic cells [7].

Detection of mutations in the synthase gene can also be used for prenatal diagnosis [8]. The mutations in uroporphyrinogen III synthase are heterogeneous, but there is one mutation (C73R) that is present in 40% of cases [9]. Homozygotes for this mutation have the most severe form of the disease; genotype-phenotype correspondence for other mutations has also been examined [2]. In addition to molecular analyses, examination of porphyrin levels should also be undertaken to assess the likely severity of the disease [10]. An elevated concentration of uroporphyrin I in the amniotic fluid is indicative of EP [8].

Fluorescence microscopy will detect fluorescing nuclei in erythrocyte precursors in EP. Histologic examinations demonstrate cutaneous changes (such as hyalinized walls of blood vessels and caterpillar bodies) that also occur in other porphyrias.


  • Treatment approaches Common treatment approaches are summarized in ( Table 2 ). Supportive care and prevention of attacks is the main treatment strategy for porphyrias.[jscimedcentral.com]
  • Treatment Edit Liver transplant has been used in the treatment of this condition.[house.wikia.com]
  • Trials of treatment for EPP have been difficult to assess. Effective treatment should reduce pain and increase time outdoors without pain.[dermnetnz.org]
  • Carotene treatment may be helpful, as it raises tolerance to sunlight. Liver and bone marrow transplantation have been successfully carried out as treatment. PCT PCT is the most common porphyria.[patient.info]


  • Prognosis In severe forms hemolytic anemia and, in particular, thrombocytopenia dominate the prognosis and greatly diminish the life expectancy of patients. The multiple fractures often cause mobility disabilities.[orpha.net]
  • What is the Prognosis of Congenital Erythropoietic Porphyria? (Outcomes/Resolutions) The prognosis of Congenital Erythropoietic Porphyria varies with the severity of the condition.[dovemed.com]
  • Prognosis Remarkable clinical variability exists in erythropoietic porphyria. Despite the limited treatments that are currently available, the prognosis is not invariably poor.[emedicine.medscape.com]
  • Prognosis A normal lifespan is possible with strict avoidance of sunlight; the usual life expectancy is 40 to 60. con·gen·i·tal e·ryth·ro·poi·et·ic por·phyr·i·a ( kŏn-jen'i-tăl ĕ-rith'rō-poy-et'ik pōr-fir'ē-ă ) Enhanced porphyrin formation by erythroid[medical-dictionary.thefreedictionary.com]
  • Liver biopsy is not helpful for estimation of prognosis of liver disease. [11] Treatment and prognosis [ edit ] There is no cure for this disorder; however, symptoms can usually be managed by limiting exposure to daytime sun and fluorescent lights.[en.wikipedia.org]


  • For porphyria etiology and pathophysiology, see Overview of Porphyrias . Resources In This Article[merckmanuals.com]
  • Etiology Congenital erythropoietic porphyria is caused by a deficiency of uroporphyrinogen- synthase (URO-S; the fourth enzyme in the heme biosynthesis pathway) leading to a massive accumulation of isomeric I porphyrins (uro and coproporphyrins) in the[orpha.net]
  • […] founder effect) Onset: puberty to age 30 years CEP: rare, 150 cases reported ( 1 ) Onset: infancy to age 10 years XLP: prevalence 1/700,000 ( 3 , 4 ) Onset: childhood HCP: rare, 1 ) Onset: after puberty ADP: rare, 1 ) Onset: both childhood and adulthood Etiology[unboundmedicine.com]
  • Etiology Erythropoietic porphyria is caused by autosomal recessive inheritance of genes that encode abnormal uroporphyrinogen III synthase (UROS) enzyme protein.[emedicine.medscape.com]
  • (Etiology) Congenital Erythropoietic Porphyria is caused by one or several mutations in the UROS gene.[dovemed.com]


  • Summary Epidemiology Since its description at the end of the 19th century, about 200 cases have been reported in the literature.[orpha.net]
  • Molecular epidemiology of erythropoietic protoporphyria in the united kingdom. Br J Dermatol. 2010;162:642–6. Minder EI, Schneider-Yin X, Steurer J, Bachmann LM.[rarediseases.org]
  • […] inheritance Deficient enzyme: no. 7 (protoporphyrinogen type III oxidase, mitochondrial, PPOX gene) X-linked protoporphyria (XLP) Chronic; X-linked dominant inheritance Gain-of-function mutation in enzyme no. 1 (ALA synthase, mitochondrial, ALAS2 gene) Epidemiology[unboundmedicine.com]
  • Epidemiology Frequency United States A porphyria registry has only recently been established in the United States ( American Porphyria Foundation ); therefore, accurate figures are not yet available.[emedicine.medscape.com]
Sex distribution
Age distribution


  • For porphyria etiology and pathophysiology, see Overview of Porphyrias . Resources In This Article[merckmanuals.com]
  • […] doi: 10.1097/MOH.0000000000000330 ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Abstract Author Information Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological[journals.lww.com]
  • Onset: puberty to age 30 years CEP: rare, 150 cases reported ( 1 ) Onset: infancy to age 10 years XLP: prevalence 1/700,000 ( 3 , 4 ) Onset: childhood HCP: rare, 1 ) Onset: after puberty ADP: rare, 1 ) Onset: both childhood and adulthood Etiology and Pathophysiology[unboundmedicine.com]
  • However, further studies to understand the actual pathophysiology of the disease are required.[ojoonline.org]
  • Pathophysiology Erythropoietic porphyria is primarily a disorder of bone marrow heme synthesis.[emedicine.medscape.com]


  • The treatment of CEP is aimed at preventing scarring of skin and eyes, and treatment of the complications mentioned above.[porphyria.eu]
  • Some or all of the following measures may be needed: Clothing: Protection of exposed skin from direct sunlight is required to prevent blistering and scarring.[skinsupport.org.uk]
  • As the rarity of disease has prevented any therapeutic trials, treatment reports have been limited to a single or a few cases.[bloodjournal.org]



  1. Gross U, Hoffmann GF, Doss MO. Erythropoietic and hepatic porphyrias. J Inherit Metab Dis. 2000 Nov;23(7):641-661.
  2. Desnick RJ, Astrin KH. Congenital erythropoietic porphyria: advances in pathogenesis and treatment. Br J Haematol. 2002 Jun;117(4):779-795.
  3. Hillenkamp J, Reinhard T, Fritsch C, et. al. Ocular involvement in congenital erythropoietic porphyria (Günther's disease): cytopathological evaluation of conjunctival and corneal changes. Br J Ophthalmol. 2001 Mar; 85(3):371
  4. Poh-Fitzpatrick MB. Clinical features of the porphyrias. Clin Dermatol. 1998 Mar-Apr;16(2):251-264.
  5. Freesemann AG, Bhutani LK, Jacob K, Doss MO. Interdependence between degree of porphyrin excess and disease severity in congenital erythropoietic porphyria (Günther's disease). Arch Dermatol Res. 1997 Apr;289(5):272-276.
  6. Tsai SF, Bishop DF, Desnick RJ. Coupled-enzyme and direct assays for uroporphyrinogen III synthase activity in human erythrocytes and cultured lymphoblasts. Enzymatic diagnosis of heterozygotes and homozygotes with congenital erythropoietic porphyria. Anal Biochem. 1987 Oct;166(1):120-133.
  7. Deybach JC, Grandchamp B, Grelier M, et al. Prenatal exclusion of congenital erythropoietic porphyria (Günther's disease) in a fetus at risk. Hum Genet. 1980 Feb;53(2):217-221.
  8. Ged C, Moreau-Gaudry F, Taine L, et. al. Prenatal diagnosis in congenital erythropoietic porphyria by metabolic measurement and DNA mutation analysis. Prenat Diagn. 1996 Jan;16(1):83-86.
  9. Frank J, Wang X, Lam HM, et al. C73R is a hotspot mutation in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria. Ann Hum Genet. 1998 May;62(Pt 3):225-230.
  10. Sassa S. Modern diagnosis and management of the porphyrias. Br J Haematol. 2006 Nov;135(3):281-292.


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