The diagnosis is made by porphyria profile study and decreased relative enzyme activity. Congenital erythropoietic porphyria genetic and rare. This is the commonest erythropoietic form of porphyria one in which it is predominantly erythroid haem synthesis which is disturbed. Other articles where congenital erythropoietic porphyria is discussed. 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. Congenital erythropoietic porphyria, or gunthers disease, is a form of erythropoietic porphyria characterized by a very severe and mutilating photodermatosis. Congenital erythropoietic porphyria most commonly presents in the first few years of life.
The primary abnormality is an almost complete absence of uros activity, previously termed uroporphyrinogen iii cosynthase. Congenital erythropoietic porphyria metabolic disorders. Congenital erythropoietic porphyria in three siblings bari a. Congenital erythropoietic porphyria due to a mutation in gata1. Congenital erythropoietic porphyria cep is characterized in most individuals by severe cutaneous photosensitivity with blistering and. Congenital erythropoietic porphyria cep is very rare metabolic disorder affecting the synthesis of haem, the ironcontaining pigment that binds oxygen onto red blood cells. These arise from deficiencies in enzymes that catalyze steps in heme biosynthesis. There are only a few families known to us in south africa carrying this condition. Clinical features include photosensitive blistering and severe anemia. Urosynthetase is the fourth enzyme in the heme biosynthesis pathway, and it normally converts hydroxymethylbilane to uroporphyrinogen iii. Erythropoietic protoporphyria porphyria for professionals. In this condition, the skin is severely sensitive to light, which often presents as scarring, blistering, and hair growth on the handsface.
It is estimated that about 1 in every 23 million people are affected by cep, which affects males and females equally, and occurs in all ethnic groups. Erythropoietic protoporphyria epp is a type of porphyria. This leads to the accumulation of toxic porphyrins, which make tissues photosensitive. Congenital erythropoietic porphyria is a rare autosomal recessive disorder that usually presents with marked skin photosensitivity, hypertrichosis, blistering, scarring, milia formation and dyspigmentation of the photoexposed areas. It is one of the most severely affected photosensitive disorders. A timely diagnosis can prevent undesirable skin findings of the disease and death due to hematological involvement before a curative allogeneic bone marrow. Congenital erythropoietic porphyria cep is a rare genetic disease resulting from the remarkable deficient activity of uroporphyrinogen iii synthase, the fourth enzyme of the haem biosynthetic. Editor,the porphyrias are a group of rare inherited disorders caused by specific enzymatic defects of the haem biosynthetic pathway. Erythropoietic protoporphyria and xlinked protoporphyria. It is estimated that about 1 in every 23 million people are affected by cep, which affects males and females equally, and occurs in all skin types. Congenital erythropoietic porphyria cep is a rare subgroup with the most severe photosensitivity and mutilation.
Congenital erythropoietic porphyria cep is the rarest type of porphyria and is commonly seen in infancy. Modern diagnosis and management of the porphyrias uw. May 24, 2018 erythropoietic porphyria is primarily a disorder of bone marrow heme synthesis. In the first, the overproduction occurs in relation to hemoglobin synthesis by cells in the bone marrow. Severe neonatal congenital erythropoietic porphyria experts. Urosynthetase is the fourth enzyme in the heme biosynthesis pathway, and it normally converts hydroxymethylbilane to. Erythropoietic protoporphyria epp european porphyria network. Erythropoietic protoporphyria is a form of porphyria, which varies in severity and can be very painful.
Erythropoietic porphyria an overview sciencedirect topics. Porphyrins, total, plasma mayo clinic laboratories. Congenital erythropoietic porphyria is inherited as an autosomal recessive genetic condition. Congenital erythropoietic porphyria cep is a rare disease characterized by erosive photosensitivity and chronic hemolysis due to a defect of the enzyme uroporphyrinogeniiisynthase uros. Other articles where erythropoietic porphyria is discussed. Woods lamp fluorescence of the diaper is a useful screening test. 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. Each porphyria is characterised by a specific partial enzyme deficiency fig 1. Erythropoietic protoporphyria genetic and rare diseases. Based on the main organ involved, the porphyria diseases are classified into hepatic. Ocular ocular manifestations of erythropoietic porphyria include blepharitis, cicatricial ectropion, and conjunctivitis. The word porphyria originated from the greek word porphura.
Congenital erythropoietic porphyria pathology britannica. Congenital erythropoietic porphyria nord national organization. Porphyria is an inherited incurable disorder resulting from the buildup of heme precursors throughout the body. Phillips jd, steensma dp, pulsipher ma, spangrude gj, kushner jp. Congenital erythropoietic porphyria is a rare form of porphyria, presenting during the neonatal period or during infancy. A rare case of puberty onset congenital erythropoietic porphyria with ophthalmological manifestations. David weedon ao md frcpa fcaphon, in weedons skin pathology third edition, 2010. Nineteen of the patients were female, fourteen were male. Congenital erythropoietic porphyria pronunciation in english. Congenital erythropoietic porphyria, cep also referred to as gunther disease is inherited as an autosomal recessive disorder.
Due to abnormally low levels of this enzyme, excessive amounts of protoporphyrin accumulate in the bone marrow, blood plasma, and red blood cells. Pdf severe neonatal congenital erythropoietic porphyria. 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. Erythropoietic protoporphyria there are approximately 20 families with erythropoietic protoporphyria in south africa. Plasma specimens from patients with active porphyria cutanea tarda, congenital erythropoietic porphyria, and erythropoietic protoporphyria may exhibit.
A 32yearold man presented with severe pain, swelling, and loss of. Congenital erythropoietic porphyria cep is also known as gunthers disease was originally named hematoporphyria by gunther in 1911, and the first published case of porphyria was probably of this type. Alas2 became more into focus as an important factor in the erythropoietic porphyrias when whatley et al 4 described xlinked dominant protoporphyria, an erythropoietic porphyria related to gainoffunction mutations in alas2, in 2008. Congenital erythropoietic porphyria cep is one of the rarest of porphyrias occurring worldwide. May 20, 2018 congenital erythropoietic porphyria cep is a rare, genetic, skin condition commonly present in young children. A rare case report jiaomr urine pink staining of the diapers in the neonatal period is common.
How to pronounce congenital erythropoietic porphyria in english. 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. Porphyrias are a group of metabolic disorders resulting from enzymatic defects in the heme biosynthetic pathway. Erythropoietic protoporphyria epp is one of a group of genetic diseases called the porphyrias. Although the chemical nature of the accumulating porphyrins in patients with cep was delineated by 1930 moore, 1990, it was not until 1969 that the specific enzyme defect in cep was. In epp there is a buildup of one particular porphyrin called protoporphyrin that is produced in excess from the bone marrow. Cep a disorder that is a member of a family of disorders referred to as the porphyrias. Erythropoietic protoporphyria epp deficient activity of ferrochelatase fech, the last enzyme in the heme biosynthetic pathway. Oral ciclopirox administration increased uroiiis activity. Porphyria is a general term for diseases caused by dep osition of intermediate products such as porphyrins in the liver or skin, as a result of congenital or.
Erythropoietic porphyria ep belongs to the porphyria group of disorders. Cep is a very rare genetic autosomal recessive disease, with mutation in the gene that codifies uroporphyrinogeniii synthase, leading to porphyrin accumulation in many tissues, with marked skin photosensitivity, hemolytic anemia with splenomegaly and a decreased life expectancy. In congenital erythropoietic porphyria, urine aminolavulanic acid and porphobilinogen are typically normal. Congenital porphyria in animals was first described by fourie and rimington1, who found the condition in cattle in south africa. Gunther disease, is a congenital form of erythropoietic porphyria. Anaesthetic management of erythropoietic protoporphyria. Anaesthetic management of erythropoietic protoporphyria anaesthetic management of erythropoietic protoporphyria torrance, john m. Congenital erythropoietic porphyria congenital erythropoietic porphyria cep is a rare cutaneous pophyria which presents with photosensitivity, complicated by presence of hemolytic anemia. 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. Next, tofigueras et al 5 described another gainoffunction mutation in alas2 causing a cep phenotype of increased.
How to pronounce congenital erythropoietic porphyria. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. It was initially described by hans gunther so is also known as gunther disease. 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 diagnosis and management of erythropoietic protoporphyria. It is, however, commonly underrecognized and can lead to both cutaneous manifestations as well as derangement in hepatic function in a minority of patients. Congenital erythropoietic porphyria british association of. Porphyria cutanea tarda is the most common porphyria. Congenital erythropoietic porphyria in three siblings bari. There is no permanent cure and the treatment is supportive. It results from an inherited deficiency of the heme biosynthetic enzyme uroporphyrinogen iii synthase uros. Erythropoietic porphyria definition of erythropoietic. It is one of the rarest cutaneous porphyrias with approximately 150 cases reported till date. Congenital erythropoietic porphyria with erythrodontia.
The major manifestations are blistering skin conditions, often severe and leading to deformities, and hemolytic anemia. A 3 dayold male baby was admitted with neonatal jaundice for phototherapy. This leads to altered patterns of synthesis of porphyrins and their precursors, which accumulate and are linked to clinical. Manifestations of the disease vary and depend on the metabolic intermediates that accumulate and the organs primarily affected. Porphyrias are a group of disorders caused by enzymatic defects in the biosynthesis of haem. Porphyria and its neurologic manifestations jennifer a. Erythropoietic protoporphyria is thought to be the second most common porphyria seen in clinical practice.
Erythropoietic protoporphyria porphyria for patients. Erythrodontia in congenital erythropoietic porphyria. May 24, 2018 congenital erythropoietic porphyria due to a mutation in gata1. Congenital erythropoietic porphyria cep is the rarest autosomal recessive porphyria resulting from a deficiency of uroporphyrinogen iii cosynthase uros, the fourth enzyme in. Both erythropoietic porphyria and chronic hepatic porphyria accompany cutaneous photosensitivity, but they are not associated with neurological symptoms. Panel for congenital erythropoietic protoporphyria and. Erythropoietic protoporphyria is caused by pathogenic variants mutations in the fech gene which. Repurposing ciclopirox as a pharmacological chaperone in a. Congenital erythropoietic porphyria cep, also called gunthers disease after the doctor who first described it, is the rarest of the porphyrias. It is characterized by severe skin photosensitivity that may lead to scarring, blistering, and increased hair growth at the face and back of the hands. Clinical manifestations include onset in infancy of blistering of sunexposed areas, atrophic scars, mutilated fingers, and bright red fluorescence of the urine and teeth. Heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. Most common erythropoietic porphyria in children after pct second most common porphyria in adults fech activities as low as 1525% of normal in lymphocytes and cultured fibroblasts. Erythropoietic protoporphyria epp is one of the less common forms of porphyrias.
It differs from the other porphyrias in several respects. Erythropoietic porphyria is primarily a disorder of bone marrow heme synthesis. Ocular involvement in congenital erythropoietic porphyria. Additionally, fecal protoporphyrin is typically mildly elevated. Congenital erythropoietic porphyia cep is the rarest of the bullous porphyrias less than 200 cases have been reported till recent times and a clinician may not. Deficient activity of the enzyme uroporphyrinogen iii synthase in erythrocyte precursor cells causes a shift of the pathway away from the isomer iii porphyrinogen production that can effect the endproduct heme. However, uroporphyrin and coproporphyrin tend to be markedly elevated and moderately elevated, respectively, in the urine more than in the feces. This staining is due to the porphyrin pigment in the urine.
Porphyrins, in combination with iron, form hemes, which in turn combine. Gunther disease, also known as congenital erythropoietic porphyria cep, uroporphyrinogen iii synthase deficiency and uros deficiency, is a congenital form. Congenital erythropoietic porphyria gunthers disease congenital erythropoietic porphyria omim 263700 is a rare, autosomal recessive disorder of heme synthesis resulting from a deficiency of uroporphyrinogen iii cosynthase urosynthase which leads to an accumulation of porphyrins, particularly. Congenital erythropoietic porphyria cep is a rare, genetic, skin condition commonly present in young children. Porphyrias are caused by an abnormality in the heme production process.
We present the results of a study of the porphyrinforming enzymes in the erythrocytes of a recently detected case of cbp, in the immediate family, and in the family of a second cousin who died in infancy with a clinical picture similar lo that seen. Erythropoietic porphyria ep, or congenital erythropoietic porphyria cep, results from a deficiency of an enzyme in the pathway for heme synthesis. Apr 11, 2018 erythropoietic protoporphyria epp is a type of porphyria. Congenital erythropoietic porphyria cep is the rarest type of. Congenital erythropoietic porphyria cep, also called gunthers disease after. The porphyrias are a heterogeneous group of metabolic disorders arising from defects in the haem biosynthetic pathway. Dyck mayo clinic, department of neurology, rochester, mn, usa introduction porphyrias are rare disorders of heme metabolism, each characterized by a defect in an enzyme required for the synthesis of heme. Congenital erythropoietic porphyria cep is a rare enzymatic disorder of heme metabolism, leading to the accumulation of porphyrins in the skin and subdermal structures. Reduced activity of this enzyme causes a buildup of the chemical protoporphyrin in the skin. Porphura actually means purple pigment, which, in suggestion, the color that the body fluid changes when a person has gunthers disease. One possible treatment was discovered when treating an individual with supplemental iron for a gastric ulcer. Erythropoietic protoporphyria epp european porphyria. The three most common porphyrias porphyria cutanea tarda pct, acute intermittent porphyria aip, and erythropoietic protoporphyria epp, in that order differ completely from each other in terms of clinical manifestations, diagnostic testing, and treatment, as discussed below.
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