Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.
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PMID:The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria. 266 29

Erythropoietic protoporphyria (EPP) is an inherited disorder of haem biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH), which catalyses the insertion of iron into protoporphyrin, the last step in haem biosynthesis. Development of clinically overt EPP usually requires inheritance of a severe FECH mutation trans to a low-expression FECH variant (FECH IVS3-48C), which is present in 13% of the U.K. population. Reduced FECH activity leads to accumulation of protoporphyrin in various tissues. An excess amount of free protoporphyrin in the skin causes photosensitivity. EPP usually presents in early childhood or infancy, with painful burning and pruritus within minutes of light exposure. Onset of symptoms in adults is rare and often associated with acquired somatic mutation of the FECH gene secondary to haematological malignancy. Here we describe a patient with EPP, in whom the presenting clinical symptom, night-time itch, did not appear until middle age and who had an asymptomatic sister with the same FECH genotype.
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PMID:Late presentation of erythropoietic protoporphyria: case report and genetic analysis of family members. 1771 25

Erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism in which decreased activity of ferrochelatase (FECH) leads to accumulation of protoporphyrin IX (PP IX) in red blood cells, plasma, liver, and bile, and increased PP IX excretion in feces. Clinically, EPP is characterized by photosensitivity that begins in early childhood and includes burning, swelling, itching, and painful erythema in sun-exposed areas. Chronic liver disease is an important complication in a minority of EPP patients, and in some cases liver transplantation has been performed. So far, about 110 different mutations and several polymorphisms have been characterized in the human FECH gene. The relationship between mutations, polymorphisms, and porphyria development in Argentinean patients was investigated. This is the first genetic study carried out in the Argentinean population. In five Argentinean EPP families we detected three novel mutations: a deletion (451delT) producing a stop codon located 18 codons downstream from the mutation and two splicing mutations: IVS1-2A>G leading to exon 2 skipping and IVS4-2A>G, which causes the loss of the first 48 bp of exon 5. We also found two previously described mutations: C343T and 400delA, which produce stop codons. All patients had an FECH activity 25% of normal and also had the polymorphisms -251A>G in the promoter region and IVS1-23 C>T and IVS3-48 T>C. Our findings provide supporting evidence for the concept that the inheritance of the low expression allele IVS3-48C in trans with a mutation in the FECH gene is necessary for EPP to become clinically manifest.
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PMID:Novel null-allele mutations and genotype-phenotype correlation in Argentinean patients with erythropoietic protoporphyria. 1969 96

A 31-year-old woman presented with recurrent swelling, burning, prickling and itching of the arms and the hands which appeared after UV exposure in the summer. Simultaneously she often had chills, malaise, nausea and circulatory problems lasting for hours. She did not have erythema or wheals. She had been seen by a number of specialties but to no avail. Her deceased mother suffered from the same symptoms. On presentation she had no skin lesions. Laboratory testing showed a dramatic increase in total protoporphyrin, enabling us to diagnose erythropoietic protoporphyria. This is a rare, genetic metabolic disturbance in hematopoiesis, whose true prevalence is probably underestimated. Because of abnormal or absent function of ferrochelatase, protoporphyrin accumulates in blood, erythrocytes and tissue usually causing photosensitivity as the first clinical symptom. The prognosis depends on the severity of liver involvement. Because of the marked restrictions on activity, especially in avoiding UV exposition, the quality of life of the patients and their families are strongly influenced. The odyssey of our patient and her mother in finding a diagnosis demonstrates impressively that the EPP is an important photosensitizing disease which must not be forgotten.
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PMID:[Erythropoietic protoporphyria. A rare differential diagnosis among photosensitive diseases]. 2280 17

Erythropoietic protoporphyria (EPP), a chronic erythropoietic porphyria, is characterized by excess accumulation of protoporphyrin, particularly in erythroid cells. EPP inheritance is complex, almost always associated with two molecular defects. In most EPP patients, clinical expression requires coinheritance of a private ferrochelatase (FECH) mutation trans- to a hypomorphic FECH*IVS3-48C allele. This leads to a decrease of FECH activity below the critical threshold. This is characterized by cutaneous photosensitivity in early childhood such as itching, burning, swelling and redness in sun-exposed areas. Hepatic failure occurs in some patients (about 1-10 % of EPP patients), which may necessitate liver transplantation. We investigated a Czech family with two patients with manifested EPP in four generations. We found a novel mutation, c.84G >A, in the FECH gene in four individuals including proband and his mother (G84A transition in exon 2; p.W28*). Both clinically manifested probands inherited the hypomorphic IVS3-48C allele as well, while two clinically latent individuals with FECH mutation did not. To address the question whether the relatively low incidence of EPP in the Czech Republic might be due to lower frequency of the IVS3-48C allele, we screened for the frequency of the low expression allele in a control Czech (West Slaves) Caucasian population. Such study has not been performed in any Slavic population. Among 312 control individuals, there were no IVS3-48C/C (c.68-23C-T) homozygotes; 35 IVS3-48C/T heterozygous individuals were detected. The frequency of IVS3-48C allele was thus found to be 5.5 % in the Czech population, comparable to most West Caucasian populations.
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PMID:A Novel Mutation in the FECH Gene in a Czech Family with Erythropoietic Protoporphyria and a Population Study of IVS3-48C Variant Contributing to the Disease. 2678 44