Preferred test to begin assessment for congenital erythropoietic porphyria and porphyria cutanea tarda and during symptomatic periods for acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria when specimen transport will not exceed 72 hours. Congenital erythropoietic porphyria definition in the. In congenital erythropoietic porphyria mice, the proteasome inhibitor bortezomib has been used with some success to reverse the premature mutant protein degradation caused by deficiency of. Porphyrias are caused by an abnormality in the heme production process. Advances in understanding the pathogenesis of congenital. Congenital erythropoietic porphyria cep, also called gunthers disease after. Congenital erythropoietic porphyria karger publishers. Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Erythropoietic porphyria is primarily a disorder of heme synthesis that occurs in the bone marrow. A rare case of puberty onset congenital erythropoietic porphyria with ophthalmological manifestations.
Chronic facial scarring, hirsutism, and fluorescent teeth, which are common in congenital erythropoietic porphyria or hepatoerythropoietic porphyria, are not usually found in epp. Congenital erythropoietic porphyria cep, gunthers disease is an extremely rare autosomal recessive disease there have been only 33 case reports in japan to date. Congenital erythropoietic porphyria british skin foundation. Congenital erythropoietic porphyria and hepatoerythropoietic porphyria. Pdf severe neonatal congenital erythropoietic porphyria. Erythropoietic protoporphyria epp is a type of porphyria. Mar 22, 2017 congenital erythropoietic porphyria cep is the rarest type of porphyria and is commonly seen in infancy. Congenital erythropoietic porphyria cep, also called gunthers disease after the doctor who described it in 1911, is an inherited disease and the rarest of the main types of porphyria, in cep the activity of an enzyme called uroporphyrinogen iii synthase uros is very low. Gunther disease, is a congenital form of erythropoietic porphyria. How is congenital erythropoietic porphyria treated. Congenital erythropoietic porphyria cep is characterized in most individuals by severe cutaneous photosensitivity with blistering and increased friability of the skin over lightexposed areas. Heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. It is one of the most severely affected photosensitive disorders. Pdf congenital erythropoietic porphyria researchgate.
Gunther disease, also known as congenital erythropoietic porphyria cep, uroporphyrinogen iii synthase deficiency and uros deficiency, is a congenital form. A 32yearold man presented with severe pain, swelling, and loss of vision in his left eye after excessive exposure. Congenital erythropoietic porphyria the american journal of. When erythropoietic protoporphyria is caused by mutations in the alas2 gene, it has an xlinked dominant pattern of inheritance. Congenital erythropoietic porphyria is an autosomal recessive condition. Congenital erythropoietic porphyria cep is a rare inherited disorder mainly due to a defect in uroporphyrinogen iii synthase uros. Congenital erythropoietic porphyria genetic and rare. Congenital erythropoietic porphyria in three siblings bari a.
A rare case report rr mahendra raj, g anuradha, mohamed abdul cader riyaz, t vijayavel abstract congenital erythropoietic porphyria belongs to the group of erythropoietic porphyria which are primarily inborn errors of bone marrow heme synthesis. In this condition, the skin is severely sensitive to light, which often presents as scarring, blistering, and hair growth on the handsface. One possible treatment was discovered when treating an individual with supplemental iron for a gastric ulcer. Congenital erythropoietic porphyria gunther disease congenital erythropoietic porphyria, or gunther disease, is one of the least common porphyrias.
Congenital erythropoietic porphyria cep congenital erythropoietic porphyria cep is a very rare inherited metabolic disorder resulting from the deficient function of the enzyme uroporphyrinogen lll cosynthase uros, the fourth enzyme in the heme biosynthetic pathway. 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. Of the porphyrias, it is the most mutilating type, usually presenting early in life. Congenital erythropoietic porphyria cep congenital erythropoietic porphyria cep is also a very rare form of porphyria inherited as an autosomal recessive trait associated with a deficiency in the enzyme activity of uroporphyrinogen cosynthetase. Onset in most affected individuals occurs at birth or early infancy. Clinical manifestations range from severe mutilation to mild erosions and blisters on sunexposed areas. 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. This leads to the accumulation of toxic porphyrins, which make tissues photosensitive. Background congenital erythropoietic porphyria cep is a rare autosomal recessive disease caused by the deficient activity of the heme biosynthetic enzyme, uroporphyrinogen iii synthase urosynthase, and the accumulation of the nonphysiologic and phototoxic porphyrin i isomers. Congenital erythropoietic porphyria cep is characterized in most individuals by severe cutaneous photosensitivity with blistering and. Repurposing ciclopirox as a pharmacological chaperone in a. Congenital erythropoietic porphyria or gunthers disease belong to the group of erythropoietic porphyrias with predominant cutaneous manifestations. Congenital erythropoietic porphyria cep is one of the rarest autosomal recessive disorders of the porphyrin metabolism caused by the homozygous defect of.
The erythropoietic porphyrias include congenital erythropoietic porphyria cep and erythropoietic protoporphyria autosomal dominant ferrochelatase deficiency. The inheritance patterns, enzymatic defects and accumulated porphyrins in the erythropoietic porphyrias are shown in table i. Congenital erythropoietic porphyria metabolic disorders. 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. Case report congenital erythropoietic porphyria gunthers. A surgeon removes the spleen in a hospital, and a patient receives general anesthesia.
The erythropoietic porphyrias include congenital erythropoietic. Pdf congenital erythropoietic porphyria cep, or gunther disease, is a rare variant of porphyria. May 20, 2018 congenital erythropoietic porphyria cep is a rare, genetic, skin condition commonly present in young children. 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. Congenital erythropoietic porphyria cep is a rare autosomal recessive disease caused by the deficient activity of the heme biosynthetic enzyme, uroporphyrinogen iii synthase urosynthase, and. Congenital erythropoietic porphyria indian pediatrics. 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.
Congenital erythropoietic porphyria, or gunther disease, is a form of erythropoietic porphyria characterized by very. Porphyrias with an autosomal recessive pattern of inheritance include alad deficiency porphyria, congenital erythropoietic porphyria, and some cases of erythropoietic protoporphyria. The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of type 1 porphyrins, and later hypertrichosis. Types of porphyria alberta canada porphyria society.
The primary abnormality is an almost complete absence of uros activity, previously termed uroporphyrinogen iii cosynthase. Congenital erythropoietic porphyria due to a mutation in gata1. This leads to increased production of porphyrins, called type i. Epp is due to an inherited deficiency of the enzyme ferrochelatase. Genebank nm000375, efforts have been made to clarify underlying mutations that cause cep. Congenital erythropoietic porphyria has been included in the chronic. How to pronounce congenital erythropoietic porphyria in english. Cep also has been termed gunther disease, erythropoietic porphyria. Congenital porphyria in animals was first described by fourie and rimington1, who found the condition in cattle in south africa. Congenital erythropoietic porphyria or gunthers disease is a rare form of cutaneous porphyria. It is autosomal recessive in nature and very few cases have been described in medical literature.
Porphyrin can be overproduced in the liver or bone marrow, therefore some authors classify porphyrias as erythropoietic or hepatic according to the main site of overproduction of heme precursors 8. Reduced activity of this enzyme causes a buildup of the chemical protoporphyrin in the skin. Patients with congenital erythropoietic porphyria cep lack normal uros activity, and as a result the hmb intermediate accumulates excessively in bone marrow red blood cell rbc precursors that are actively synthesizing hemoglobin. Two brothers with mild congenital erythropoietic porphyria. Each subtype results from deficient activity of a specific enzyme in the heme biosynthetic pathway. Erythropoietic protoporphyria epp is one of a group of genetic diseases called the porphyrias. Congenital erythropoietic porphyria cep, also known as gunthers disease, is a metabolic disease caused by a transformation in the gene that codifies uroporphyrinogen. Congenital erythropoietic porphyria cep is a rare subgroup. Congenital erythropoietic porphyria cep, also called gunthers disease after the doctor who first described it, is the rarest of the porphyrias. Most other forms of genetic porphyria are dominantly inherited 120, 176000, 176100, 176200.
Congenital erythropoietic porphyria cep is a rare, genetic, skin condition commonly present in young children. This porphyria is due to deficiency of uroporphyrinogen iii cosynthase and accumulation of hmv which is converted non enzymatically to uroporphyrinogen i. Case report congenital erythropoietic porphyria associated. Congenital erythropoietic porphyria austin publishing group. Neither we nor the doctors had any idea what was ahead of us. Therapeutic potential of proteasome inhibitors in congenital. Need for measurement of porphyrins in teardrops in patients. A 3 dayold male baby was admitted with neonatal jaundice for phototherapy.
The cause of this disease is the deficient activity of uroporphyrinogen iii synthase uros. A fourteen year old girl with classic congenital erythropoietic porphyria has recurrent skin bullae, mutilating scarring of the face and hands, hirsutism. Congenital erythropoietic porphyria british association of. Porphura actually means purple pigment, which, in suggestion, the color that the body fluid changes when a person has gunthers disease. Congenital erythropoietic porphyria cep is the rarest type of porphyria and. Congenital erythropoietic porphyria cep is the rarest type of porphyria and is commonly seen in infancy. Analytical sensitivity is 99% as all reported variants are detectable by this method. Without warning, i was told that oliver needed to be born early due to complications with little to no amniotic fluid.
Severe neonatal congenital erythropoietic porphyria. Congenital erythropoietic porphyria cep is one of the rarest autosomalrecessive disorders of the porphyrin metabolism caused by the homozygous defect of. Erythropoietic porphyria ep, or congenital erythropoietic porphyria cep, results from a deficiency of an enzyme in the pathway for heme synthesis. Editor,the porphyrias are a group of rare inherited disorders caused by specific enzymatic defects of the haem biosynthetic pathway. The word porphyria originated from the greek word porphura. 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 protoporphyria genetic and rare diseases. It is a rare, autosomal recessive metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase.
The disease affects many organs, can be lifethreatening, and currently lacks curative treatments. There is no permanent cure and the treatment is supportive. Sep 14, 2019 congenital erythropoietic porphyria cep. Nineteen of the patients were female, fourteen were male. People with congenital erythropoietic porphyria or hepatoerythropoietic porphyria may need surgery to remove the spleen or blood transfusions to treat anemia. Congenital erythropoietic porphyria is a rare autosomal recessive disease produced by deficient activity of uroporphyrinogen iii synthase, the fourth enzyme in the heme biosynthetic pathway. Congenital erythropoietic porphyria is caused by a deficiency of uroporphyrinogen synthase uros. Congenital erythropoietic porphyria with erythrodontia. The development of dentition can also be affected by a number of systemic factors and metabolic diseases such as porphyria. Congenital erythropoietic porphyria cep, or gunther disease, is a rare bullous porphyria, with a uk prevalence of 1 in 3 million. Congenital erythropoietic porphyria cep is very rare metabolic disorder affecting the synthesis of haem, the ironcontaining pigment that binds oxygen onto red blood cells. The most common type of porphyria is porphyria cutanea tarda. The rarest is congenital erythropoietic porphyria c.
The major manifestations are blistering skin conditions, often severe and leading to deformities, and hemolytic anemia. Congenital erythropoietic porphyria, an autosomal recessive disease, is characterized by deficiency of uroporphyrinogen iii synthase. Congenital erythropoietic porphyria cep is a very rare inherited metabolic disorder resulting from the deficient function of the enzyme uroporphyrinogen iii synthase uros, the fourth enzyme in the heme biosynthetic pathway. Urosynthetase is the fourth enzyme in the heme biosynthesis pathway, and it normally converts hydroxymethylbilane to uroporphyrinogen iii. The diagnosis and management of erythropoietic protoporphyria. What is the pathophysiology of congenital erythropoietic. How to pronounce congenital erythropoietic porphyria. Congenital erythropoietic porphyria cep is an extremely rare autosomal recessively inherited disorder of the haem synthesis pathway first described by gunther in 1911. Urosynthetase is the fourth enzyme in the heme biosynthesis pathway, and it normally converts hydroxymethylbilane to.
It is panethnic, although like other autosomal recessive conditions prevalence is increased in communities where consanguinity is common. Clinical variability of the disease is related to the. Congenital erythropoietic porphyria cep is a rare sub group. What is the cause of congenital erythropoietic porphyria. Listen to the audio pronunciation in the cambridge english dictionary. Congenital erythropoietic porphyria congenital erythropoietic porphyria cep is a rare cutaneous pophyria which presents with photosensitivity, complicated by presence of hemolytic anemia. Acute hepatic porphyria is apparently recessive see 125270 as would be expected for an enzyme deficiency, autosomal recessive inheritance of congenital erythropoietic porphyria is well documented, with multiple sib cases. Erythropoietic porphyria an overview sciencedirect topics. Thats a protein in red blood cells that carries oxygen from the lungs to the rest of. In a series of unrelated patients with congenital erythropoietic porphyria, pathogenic variants in the uros gene were identified in 24 of 27 cases katugampola et al. Each type of porphyria has the same root cause a problem with making heme. May 24, 2018 congenital erythropoietic porphyria due to a mutation in gata1. Congenital erythropoietic porphyria cep is a rare genetic disease resulting.