Erythropoietic porphyria (EP) is a rare inborn error of porphyrin-heme synthesis inherited that is as an autosomal recessive trait. Congenital erythropoietic porphyria (CEP; OMIM #, also called Günther disease) is a rare, autosomal recessive porphyria. It results from. Gunther disease, also known as congenital erythropoietic porphyria (CEP), uroporphyrinogen III synthase deficiency and UROS deficiency, is a congenital form.
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CC HPO: The porphyrias are diseases caused by defects in heme synthesis, resulting in the accumulation and porpbyria excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver Gross erythropoitic al. Desnick and Astrin provided a comprehensive review of congenital erythropoietic porphyria pathogenesis and treatment. One patient with a phenotype suggestive of congenital erythropoietic anemia was erythro;oietic to have a mutation in the GATA1 gene The most dramatic form of genetic porphyria is that which was early recognized as an inborn error of metabolism by Gunther Dean, It is associated with lifelong overproduction of series Cogenital porphyrins which circulate and are deposited in many tissues, causing light-sensitization and severe damage to skin beginning in childhood.
Blistering and scarring of exposed areas may lead to mutilating deformity. Hypertrichosis is sometimes severe. Uroporphyrin I and coproporphyrin I are found in plasma, red blood cells, urine, and feces. Red urine may be observed eruthropoietic infancy, and the teeth become stained red. Hemolytic anemia, an additional complication, may be helped by splenectomy Meyer and Schmid, Gunther called this condition congenital haematoporphyria. In the newborn period the patient developed intense jaundice with hepatosplenomegaly associated with diffuse bleeding and thrombocytopenia.
On the tenth day of life the baby showed a rash with blisters on the backs of the hands and red discoloration of the urine.
Porphyria was established by high levels of porphyrins in the urine, feces, and blood. During the next 2 years transfusions were required because of hemolysis. Skin photosensitivity with blistering, fragility, hypertrichosis of the face, and erythrodontia developed. Somatic and mental development were poor. Each of the 2 forms of porphyria was established by enzymatic study. The biologic features of coproporphyria predominated during the first days of life.
A beneficial effect of hematin therapy was observed. Persistent thrombocytopenia unresponsive to corticosteroids and immunoglobulin necessitated a splenectomy. Photosensitivity, hemolytic anemia, and hypersplenism are prominent features of adult-onset Gunther disease and thrombocytopenia had been documented in several cases.
In the patient reported by Murphy et al. Four weeks following splenectomy, the platelet count rose and stabilized and remained stable 1 year later. Congenital erythropoietic porphyria is an autosomal recessive condition. Most other forms of genetic porphyria are dominantly inherited, Acute hepatic porphyria is apparently recessive see As would be expected for an enzyme deficiency, autosomal recessive inheritance of congenital erythropoietic porphyria is well documented, with multiple sib cases and increased consanguinity in parents; obligate heterozygotes have intermediate levels of uroporphyrinogen III cosynthetase activity Romeo et al.
The patient described by Nordmann et al. The patient described by Pollack and Rosenthal was the offspring of first-cousin parents and showed organomegaly, hemolytic anemia, thrombocytopenia, and cutaneous blisters.
Pollack and Rosenthal illustrated the diagnosis of this disorder in a neonate by examining a urine-soaked diaper under Wood’s light. Urine and feces of patients contain increased levels of uroporphyrinogen I and coproporphyrinogen I Gross et al. Uroporphyrinogen III cosynthetase is expressed in cultured amniotic cells so that prenatal diagnosis is possible Deybach et al.
Since the chromosomal assignment and molecular genetics of congenital erythropoietic porphyria have been determined, prenatal diagnosis by genetic analysis is possible Lim and Cohen, Iron overload was mitigated by slow infusions of deferoxamine. In a man in his mid-fifties, Pimstone et al.
Measurements of subnormal red cell uroporphyrinogen decarboxylase activity and urinary, fecal, and plasma porphyrin analyses in this patient and his 7 children indicated classic features of familial porphyria cutanea tarda They concluded that their patient had an atypical form of congenital erythropoietic porphyria similar to that described by Eriksen and Eriksen The authors pointed out that the usefulness of charcoal therapy in photocutaneous porphyrias other than this form and in reversing the hepatic lesion in patients with protoporphyric liver disease remains to be explored.
Subtle complications of long-term charcoal ingestion, such as nutrient malabsorption or systemic absorption of charcoal, require further evaluation.
They demonstrated long-term biochemical and clinical effectiveness of BMT performed in a severely affected, transfusion-dependent month-old female with CEP. Three years post-BMT, the recipient had normal hemoglobin, markedly reduced urinary uroporphyrin excretion, and no cutaneous lesions despite unlimited exposure to sunlight.
The long-term effectiveness of BMT in their patient provided the rationale for future hematopoietic stem cell gene therapy in severely affected patients. Deficiency of the enzyme uroporphyrinogen III cosynthetase was demonstrated in peripheral blood Levin, ; Romeo and Levin, and cultured fibroblasts Romeo et al. In a patient with Gunther disease, Deybach et al. Congenital erythropoietic porphyria is exceedingly rare; as ofabout cases had been reported Fritsch et al.
An analogous disorder has been described in several animal species; the best-delineated animal model is in cattle, in which autosomal recessive inheritance is well demonstrated Watson et al.
All fox squirrels Sciurus niger exhibit a species characteristic resembling congenital erythropoietic porphyria in humans Levin and Flyger Flyger and Levin noted that this appears to be the only mammalian species that possesses this characteristic except as a rare pathologic condition.
However, the condition in fox squirrels is accompanied by neither skin lesions nor hemolytic anemia. Mice homozygous for all 3 mutations were fetal lethals, except for those homozygous for a spontaneous recombinant allele. The mice showed marked porphyrin I isomer accumulation in erythrocytes, bone, tissues, and excreta and had fluorescent erythrodontia, hemolytic anemia with reticulocytosis and extramedullary erythropoiesis, and, notably, the characteristic light-induced cutaneous involvement.
These mice provided insight into why congenital erythropoietic porphyria is an erythroid porphyria and should facilitate studies of the disease pathogenesis and therapeutic endeavors. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells HSCs from the mouse model Uros mut resulted in a complete and long-term enzymatic, metabolic, and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells.
The results demonstrated the cure of this mouse model of CEP at a moderate transduction level, thus providing proof of concept of a gene therapy in this disease by transplanting genetically modified hematopoietic stem cells. Uroporphyrinogen III synthase knock-in mice have the human congenital erythropoietic porphyria phenotype, including the characteristic light-induced cutaneous lesions.
Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria Gunther’s disease. Congenital erythropoietic porphyria Gunther’s disease: Prenatal exclusion of congenital erythropoietic porphyria Gunther’s disease in a fetus at risk. Urinary excretion of position isomers of penta- and hexa-carboxylated porphyrins belonging to the isomer III series in a case of congenital erythropoietic porphyria.
Animal model of human disease: Congenital porphyria in the domestic cat Felis catus: Erythropoietic and hepatic porphyrias. The Metabolic Basis of Inherited Disease.
Congenital erythropoietic porphyria (CEP)
Uroporphyrinogen III cosynthetase in bovine erythropoietic porphyria. Uroporphyrinogen III cosynthetase activity in the fox squirrel Sciurus niger. Erythropoietic porphyria of the fox squirrel Sciurus niger.
Adult-onset congenital erythropoietic porphyria Gunther’s disease presenting with thrombocytopenia. Coexistent hereditary coproporphyria and congenital erythropoietic porphyria Gunther disease. Therapeutic efficacy of oral charcoal in congenital erythropoietic porphyria. Complete suppression of the symptoms of congenital erythropoietic porphyria by long-term treatment with high-level transfusions.
Orphanet: Congenital erythropoietic porphyria
Diaper diagnosis of porphyria. Hematin therapy in late onset congenital erythropoietic porphyria.
Effective gene therapy of mice with erythrpoietic erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells. Uroporphyrinogen III cosynthetase in asymptomatic carriers of congenital erythropoietic porphyria.
Uroporphyrinogen III cosynthetase activity in fibroblasts from patients with congenital erythropoietic porphyria. Uroporphyrinogen III cosynthetase cojgenital human congenital erythropoietic porphyria.
Congenital erythropoietic porphyria successfully treated by allogeneic bone marrow transplantation. Coupled-enzyme and direct assays for uroporphyrinogen III synthase activity in human erythrocytes and cultured lymphoblasts: Some studies of the comparative biology of human and bovine porphyria erythropoietica. Molecular basis of congenital erythropoietic porphyria: A number sign is used with this entry because congenital erythropoietic porphyria CEP is caused by homozygous or compound heterozygous mutation in the uroporphyrinogen III synthase gene UROS; on chromosome 10q A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.
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Gunther disease – Wikipedia
Adult-Onset Form Deybach et al. Prenatal Diagnosis Uroporphyrinogen III cosynthetase is expressed in cultured amniotic cells so that prenatal diagnosis is possible Deybach et al. Marver and Schmid ; Romeo et al. OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
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