Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0349506 (photosensitivity)
 4,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism, in which reduced activity of the enzyme ferrochelatase leads to accumulation of protoporphyrins in erythrocytes. Protoporphyrins are photoactivated by ultra-violet light causing tissue damage by release of free oxygen radicals, which manifests as photosensitivity. The majority of cases of erythropoietic protoporphyria present in childhood although sometimes symptoms are delayed until the second decade. We report here a case presenting in adulthood and discuss the risk of liver disease in the condition.
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PMID:Erythropoietic protoporphyria presenting in an adult. 756 35

Erythropoietic protoporphyria is an autosomal inherited disease characterized by decreased ferrochelatase activity. This abnormality results in excess protoporphyrin accumulation not only in red blood cells but also in other organs such as skin, and causes various degrees of skin photosensitivity according to degrees of decreased ferrochelatase activity. An excess protoporphyrin accumulation in liver results in severe liver damage which might cause juvenile death in some patients. Clinical views including its diagnosis and treatment are briefly summarized, and possible relationship between skin porphyrin level and skin photosensitivity is discussed.
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PMID:[Erythropoietic protoporphyria]. 761 60

Erythropoietic protoporphyria is caused by inherited deficiency of the haem synthetic enzyme ferrochelatase, and is characterized by lifelong photosensitivity. About 5% of patients also develop rapidly progressive liver failure. Inheritance is considered to be autosomal dominant, with transmission of a single ferrochelatase defect from one parent. We describe a family in which two siblings with protoporphyria suffered from severe photosensitivity and developed hepatic failure requiring liver transplantation. Their asymptomatic parents were heterozygous for distinct ferrochelatase gene mutations (exon 10 donor site a(+3)-->g and 1088T-->G). Both mutations disrupt splicing of the transcript and cause partial deficiency of ferrochelatase. The affected offspring were compound heterozygotes for these mutations. These patients suffered from an autosomal recessive form of protoporphyria characterized by severe photosensitivity and cholestatic liver disease in adolescence. We postulate that hepatic failure in erythropoietic protoporphyria may in some cases represent an autosomal recessive type of ferrochelatase deficiency distinct from the purely dermatological disorder. Studies of disease inheritance in families affected by protoporphyria may help identify those predisposed to develop severe liver complications, a distinction not currently possible.
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PMID:Autosomal recessive erythropoietic protoporphyria: a syndrome of severe photosensitivity and liver failure. 764 40

Erythropoietic protoporphyria (EPP), attributable to deficiency of ferrochelatase activity (FECH), is characterised mainly by cutaneous photosensitivity. To define the molecular defect in two EPP-affected siblings and their parents in a Swiss family, ferrochelatase cDNA was amplified by the polymerase chain reaction (PCR) and subjected to sequence analysis. A 5-bp deletion (T580-G584) was identified on one allele of the ferrochelatase gene in both patients and their mother. Screening of the mutation among family members of RsaI digestion of PCR-amplified genomic DNA revealed autosomal dominant inheritance associated with abnormal protoporphyrin concentration and enzyme activity. We also isolated ferrochelatase cDNAs containing a 18-bp insertion (part of the intron 2 sequence) between exons 2 and 3; this corresponded to six extra amino acids (YESNIR) inserted between Arg-65 and Lys-66 of the known ferrochelatase. This isoform was identified initially in mRNAs derived from both alleles of the ferrochelatase gene in one patient. Its existence was confirmed in six additional EPP patients, in five out of seven controls, and in four different cell lines (fibroblast, muscle, hepatoma and myelogenous leukaemia). This isoform, roughly 20% of the total ferrochelatase mRNA, was generated through splicing at a second donor site in intron 2 and its presence was not linked to EPP.
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PMID:Human ferrochelatase: a novel mutation in patients with erythropoietic protoporphyria and an isoform caused by alternative splicing. 770 34

Erythropoietic protoporphyria (EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase, the terminal enzyme of the haem biosynthetic pathway, which catalyses the insertion of iron into protoporphyrin to form haem. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell protoporphyrin levels. Although the majority of papers and reviews have classified EPP as an autosomal dominant disorder, the inheritance has now been shown to be more complex, and both autosomal dominant and recessive patterns of inheritance have been demonstrated using ferrochelatase activity. Further molecular studies should clarify the exact mode of inheritance. It seems likely that in the majority of families a defective allele from the apparently normal parent will be required for disease expression, but another possibility is autosomal dominant inheritance with low clinical penetrance. Exposure to bright sunlight, for as little as a few minutes in the worst affected patients, causes burning pain in exposed skin, which may be so severe and persistent that it prevents sleep for several nights. Patients usually attempt to relieve the pain by cold water or cold compresses. Apart from sun avoidance, the mainstay of prophylactic treatment has been beta-carotene. Although the published evidence for the effectiveness of beta-carotene is impressive, no controlled trials using adequate doses have been performed to unequivocally confirm its usefulness. The most serious complication of EPP is acute hepatic failure, which is due to accumulation of protoporphyrin in the liver. If jaundice develops, a rapidly fatal outcome often follows, unless liver transplantation is undertaken. Regular monitoring of liver function and red cell porphyrin levels is advisable, but this does not always identify patients before serious liver damage has occurred. Even when patients are identified at an early stage in the development of liver disease the therapeutic options available to prevent further damage are limited, and have not been fully evaluated. The gene for ferrochelatase has been cloned, sequenced and mapped to the long arm of chromosome 18. As mutations continue to be identified, phenotype/genotype correlations should become apparent, and it may eventually be possible to identify those patients at risk of developing hepatic failure. In addition, as the basic enzymatic defect in EPP is at the level of the bone marrow stem cells, which are the target cells of choice in the development of retroviral-mediated gene transfer, definitive treatment of EPP by gene therapy is a distinct hope for the future.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Erythropoietic protoporphyria. 873 51

Erythropoietic protoporphyria is characterised by skin photosensitivity and deficiency of ferrochelatase; fatal liver disease occurs rarely. Transmission is considered to be dominant with incomplete penetrance. We investigated a family in which two siblings with erythropoietic protoporphyria developed hepatic failure that required transplantation. Their healthy parents had partial enzyme deficiency and were each heterozygous for a distinct mutation in a ferrochelatase gene. Both offspring were compound heterozygotes with ferrochelatase deficiency. Recessive transmission of protoporphyria predisposes to severe liver disease in this family. Patients with the recessive form of this disease may be at special risk of hepatic failure.
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PMID:Recessive inheritance of erythropoietic protoporphyria with liver failure. 791 84

Protoporphyria is a genetic disorder characterized by a defect in the enzyme ferrochelatase, which catalyzes the chelation of iron to protoporphyrin. This causes excessive accumulation and excretion of protoporphyrin. The predominant clinical feature is photosensitivity. Progressive and fatal liver disease occurs in a small percentage of cases. We report our experience with eight patients with end-stage protoporphyric liver disease in whom a syndrome developed before transplantation that resembled the neurological crises of the acute porphyrias. This syndrome was characterized by abdominal pain, hypertension, tachycardia, extremity pain and weakness, constipation and nausea and vomiting. Erythrocyte and serum protoporphyrin levels were markedly increased in all patients. In one patient, profound hemolysis developed during the anhepatic phase of transplantation and continued over a period of 72 hr, causing an extreme increase in the serum protoporphyrin level. Progressive weakness deteriorated to paralysis in this patient. This phenomenon suggests that protoporphyrin may gain access to neural tissue when serum levels are markedly increased, causing neurotoxicity.
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PMID:Evidence for neurological dysfunction in end-stage protoporphyric liver disease. 798 71

Variegate porphyria (VP), a low-penetrant autosomal dominant inherited disorder of haem metabolism, is characterised by photosensitivity (Fig. 1) and a propensity to develop acute neuropsychiatric attacks with abdominal pain, vomiting, constipation, tachycardia, hypertension, psychiatric symptoms and, in the worst cases, quadriplegia. Acute attacks, often precipitated by inappropriate drug therapy, are potentially fatal. While earlier workers thought the distal haem biosynthetic enzyme ferrochelatase may be involved in the genesis of VP, it was shown in the early 1980's, and is now accepted, that VP is associated with decreased protoporphyrinogen oxidase activity (PPO) (E.C.1.3.3.4). VP prevalence is much higher in South Africa than elsewhere; probably due to a founder effect with patients descending from a 17th century Dutch immigrant. PPO cDNAs from Bacillus subtilis, Myxococcus xanthus, human placenta and mouse liver have been cloned, sequenced and expressed. Human and mouse cDNAs consist of open reading frames 1431 nucleotides long, encoding a 477 amino acid protein. The human PPO gene contains thirteen exons, spanning approximately 4.5 kb. We have identified a C to T transition in codon 59 (in exon 3) resulting in an arginine to tryptophan substitution (R59W). A protein expressed from an in vitro-mutagenized PPO construct exhibits substantially less activity than the wild type. The R59W mutation was present in 43 of 45 patients with VP from 26 of 27 South African families investigated, but not in 34 unaffected relatives or 9 unrelated British patients with PPO deficiency. Since at least one of these families is descended from the founder of South African VP, this defect may represent the founder gene defect associated causally with VP in South Africa.
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PMID:A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. 867 6

Partial deficiency of the last enzyme of haem biosynthesis, ferrochelatase, leads to a distinct syndrome of photosensitivity caused by overproduction of protoporphyrin by erythropoietic tissue. Erythropoietic protoporphyria has an indeterminate pattern of inheritance and may be complicated by fulminating liver disease. The recent development of simple assays for ferrochelatase activity and cloning of the human ferrochelatase gene promises to shed light on the transmission of this disorder and may allow clinical expression of disease to be predicted. This review surveys the pathological features, genetics and treatment of porphyria.
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PMID:Erythropoietic protoporphyria. 921 Nov 98

Human protoporphyria results from mutations in the ferrochelatase gene. Heritable deficiency of ferrochelatase causes overproduction of protoporphyrin IX, principally in the erythron. Photosensitivity is a universal feature of protoporphyria but hepatic clearance of the hydrophobic protoporphyrin molecule with excretion in bile may lead to precipitation within biliary pathways. Thus cholestatic injury and protoporphyrin gallstones occur. Minor hepatic abnormalities are frequent, but at least 30 patients have been reported with a progressive liver disease that requires transplantation. Fulminant hepatic disease appears to be recessively inherited in some pedigrees. Hazards of liver transplantation include tissue photolysis, hemolysis, and an unexplained neurological syndrome, but most of the 15 patients reported after transplantation have survived for several months to > 6 years. Aspects of protoporphyria, its pathogenesis and contemporary therapeutic strategies are considered, with emphasis on hepatic sequelae.
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PMID:Protoporphyria. 987 59


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