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 .
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 . Hypertrichosis of the face is also common. Damage to the eye  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 .
Entire Body System
Gov't MeSH terms 5-Aminolevulinate Synthetase/genetics* 5-Aminolevulinate Synthetase/metabolism Amino Acid Sequence Anemia, Sideroblastic/genetics Anemia, Sideroblastic/metabolism Anemia, Sideroblastic/pathology Base Sequence Child, Preschool Electrophoresis [ncbi.nlm.nih.gov]
Complete blood count showed mild anemia; Hb-9.2 mg/dl, total leucocyte count-8,200 and platelet count of 1.4 lac/cumm. On peripheral smear anemia was microcytic, hypochromic in type. [doi.org]
- Short Stature
stature Decreased body height Small stature [ more ] 0004322 Vertebral compression fractures Compression fracture 0002953 Showing of 40 Last updated: 6/1/2019 The resources below provide information about treatment options for this condition. [rarediseases.info.nih.gov]
- Pediatric Disease
In Biochemical and Molecular Basis of Pediatric Disease. Fourth edition. Edited by DJ Dietzen, MJ Bennett, ECC Wong. AACC Press 2010, pp 307-324 2. Nuttall KL, Klee GG: Analytes of hemoglobin metabolism-porphyrins, iron and bilirubin. [mayomedicallaboratories.com]
Hunt, Photosensitivity and Photoreaction, Therapy in Pediatric Dermatology, 10.1007/978-3-319-43630-2_21, (361-375), (2016). [doi.org]
Here, we describe a case of CEP with infancy onset blistering, photosensitivity, red colored urine and teeth along with scarring but without any feature of hemolysis. [doi.org]
An eleven month old female child, born of a primigravida mother of non-consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. [doi.org]
During early childhood, all the siblings started showing signs of photosensitivity with darkening of urine color followed by skin blistering over the face and hands. [ncbi.nlm.nih.gov]
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. [symptoma.com]
The oldest showed severe sclerodermiform mutilation and the youngest exhibited an initial involvement with hypertrichosis. None of them had any history of convulsions, acute abdominal pain or joint pain. [ncbi.nlm.nih.gov]
- Skin Lesion
Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues, leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity, and mutilating skin lesions. [ncbi.nlm.nih.gov]
Additionally, porphyrias may present with skin lesions or photosensitivity. [doi.org]
- 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. [ncbi.nlm.nih.gov]
The cutaneous manifestations are similar to those in PCT. They can be the only clinical features of these mixed porphyrias. [patient.info]
- Red Urine
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. [ncbi.nlm.nih.gov]
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]
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 . 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 .
Both direct and coupled assays for uroporphyrinogen III synthase activity have been developed . Prenatal diagnosis can be performed by measuring uroporphyrinogen III synthase enzyme activity in chorionic villi or cultured amniotic cells .
Detection of mutations in the synthase gene can also be used for prenatal diagnosis . The mutations in uroporphyrinogen III synthase are heterogeneous, but there is one mutation (C73R) that is present in 40% of cases . Homozygotes for this mutation have the most severe form of the disease; genotype-phenotype correspondence for other mutations has also been examined . In addition to molecular analyses, examination of porphyrin levels should also be undertaken to assess the likely severity of the disease . An elevated concentration of uroporphyrin I in the amniotic fluid is indicative of EP .
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.
- Pericardial Calcification
The cause of pericardial calcification could be deposition of porphyrins in the pericardium. Surgical importance of this rare condition is highlighted. [ncbi.nlm.nih.gov]
- Soft Tissue Calcification
The authors describe a 15-year-old boy in whom the radiologic manifestations of this disorder included the known features of osteopenia, acro-osteolysis, soft-tissue calcifications and widening of the diploic space, as well as the previously unreported [ncbi.nlm.nih.gov]
- Pink Urine
We describe a successful pregnancy in a patient with congenital erythropoietic porphyria.The patient presented at 3 months of age with pink urine and severe photosensitivity; congenital erythropoietic porphyria was diagnosed on the basis of analysis of [nejm.org]
urine 0032001 Scleroderma 0100324 Short stature Decreased body height Small stature [ more ] 0004322 Vertebral compression fractures Compression fracture 0002953 Showing of 40 Last updated: 6/1/2019 The resources below provide information about treatment [rarediseases.info.nih.gov]
During his first month of life, he was found to have pink urine. He was evaluated by a pediatric nephrologist who found no abnormalities. When his teeth began to erupt, they were noted to be dark blue. [nature.com]
We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. [ncbi.nlm.nih.gov]
8, 14, 15] Consultations A dermatologist may be consulted regarding sun avoidance measures and the treatment of secondary skin infections. [emedicine.medscape.com]
Astrin, Congenital erythropoietic porphyria: advances in pathogenesis and treatment, British Journal of Haematology, 117, 4, (779-795), (2002). [doi.org]
Congenital erythropoietic porphyria (CEP) is an autosomal recessive photomutilating porphyria with onset usually in childhood, where haematological complications determine prognosis. [ncbi.nlm.nih.gov]
Summary Background Congenital erythropoietic porphyria (CEP) is an autosomal recessive photomutilating porphyria with onset usually in childhood, where haematological complications determine prognosis. [doi.org]
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]
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) Congenital Erythropoietic Porphyria is caused by one or several mutations in the UROS gene. [dovemed.com]
Etiology Erythropoietic porphyria is caused by autosomal recessive inheritance of genes that encode abnormal uroporphyrinogen III synthase (UROS) enzyme protein. [emedicine.medscape.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]
Hand, Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology, International Journal of Dermatology, 52, 12, (1464-1480), (2013). [doi.org]
For porphyria etiology and pathophysiology, see Overview of Porphyrias. Resources In This Article [merckmanuals.com]
0000000000000330 ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Abstract Author Information Authors Article Metrics Metrics 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]
We previously demonstrated that the UROS(C73R) mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. [ncbi.nlm.nih.gov]
The treatment of CEP is aimed at preventing scarring of skin and eyes, and treatment of the complications mentioned above. [porphyria.eu]
- Gross U, Hoffmann GF, Doss MO. Erythropoietic and hepatic porphyrias. J Inherit Metab Dis. 2000 Nov;23(7):641-661.
- Desnick RJ, Astrin KH. Congenital erythropoietic porphyria: advances in pathogenesis and treatment. Br J Haematol. 2002 Jun;117(4):779-795.
- 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
- Poh-Fitzpatrick MB. Clinical features of the porphyrias. Clin Dermatol. 1998 Mar-Apr;16(2):251-264.
- 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.
- 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.
- 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.
- 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.
- 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.
- Sassa S. Modern diagnosis and management of the porphyrias. Br J Haematol. 2006 Nov;135(3):281-292.