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)

Protoporphyria (PP) is an inherited disorder of porphyrin metabolism in man in which there is excessive accumulation and excretion of protoporphyrin. Recently, a similar disorder has been described in cattle. In this report, the clinical, biochemical, and genetic features of bovine and human PP are compared. Human and bovine PP are characterized by photosensitivity and elevation of erythrocyte and fecal protoporphyrin levels. In both disorders, a deficiency of heme synthase activity is present in all tissues which have been examined. The diseases differ clinically in that hepatobiliary disease has been found thus far only in human PP. They also have different inheritance patterns. Human PP is an autosomal dominant disease, while initial studies strongly suggest that there is an autosomal recessive pattern of inheritance in bovine PP.
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PMID:Comparison of human and bovine protoporphyria. 39 59

The heterogeneous group of diseases called the porphyrias may all be characterised by derangement of specific stages in the haem biosynthetic pathway. In the acute porphyrias; acute intermittent porphyria, urophorphyrinogen 1 synthase, hereditary coproporphyria, coproporphyrinogen oxidase and variegate porphyria, ferrochelatase or protoporphyrinogen oxidase, are the enzymes affected, whilst in the non acute porphyrias, cutaneous hepatic porphyria, uroporphyrinogen decarboxylase, congenital porphyria, uroporphyrinogen cosynthase; and erythropoietic protoporphyria; ferrochelatase are the enzymes affected. In each of the porphyrias, the activity of the initial and rate controlling enzyme of the pathway, delta-aminolaevulinic acid synthase is raised which constitutes the principal control point of the pathway. Secondary control in each of these diseases lies at the leve of uroporphyrinogen 1 synthase. As a consequence of this secondary control, there is excessive excretion of the porphyrin precursors delta-aminolaevulinic acid and porphobilinogen in the acute porphyrias and excessive excretion of porphyrins leading to solar photosensitivity in the non-acute porphyrias and in variegate and hereditary coproporphyria. There are a number of secondary metabolic aspects in the porphyrias, such as the role of steroid metabolism; the influence of drugs in the potentiation of attacks; and the potential for the pathway to branch at stages prior to porphyrin formation which result in the synthesis of various monopyrroles. The therapy of the two groups of porphyrias are quite different. Prophylaxis is important in both types but is particularly important in the avoidance of various drugs in the acute porphyrias. The acute attack may be specifically treated with carbohydrates, beta-blockers and haematin. Cutaneous hepatic porphyria may be treated by venesection, erythropoietic protoporphyria with beta caratene whilst congenital porphyria may be improved by splenectomy and chloroquine therapy.
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PMID:The porphyrias. 39 1

The photodermatosis in erythropoietic protoporphyria (EPP) is caused by the accumulation of photosensitizing protoporphyrin (PP) in the skin, due to a defect in ferrochelatase, the enzyme that inserts ferrous iron into PP to form heme. Hydroxyl radical (.OH) and singlet oxygen generation with subsequent lipid peroxidation are thought to play a major role in the pathogenesis of the photodermatosis in EPP. Hydrogen peroxide (H2O2) can generate .OH in the Haber-Weiss as well as the Fenton reaction, and is thus a potentially harmful intermediate in the photoreduction of O2. The use of oxyradical scavengers, such as beta-carotene, has been reported to be beneficial in the treatment of EPP photodermatosis. In this study, N-acetylcysteine (NAC) 1800 mg/day was used for 3 reasons: (i) its -SH groups directly scavenge H2O2; (ii) ferrochelatase can be activated by sulfhydryl groups; (iii) NAC was reported to upregulate the glutathione redox system, which is a major endogenous anti-oxidant system. However, in a double-blind crossover placebo controlled study on 6 EPP patients, we could neither demonstrate an effect through photosensitivity tests, nor on light hypersensitivity as reported by the patients. This dosage of NAC could not increase reduced glutathione and did not affect the red blood cell PP content nor the excretion of PP in the feces. Neither were adverse effects observed. We conclude that the oral administration of NAC, in the relatively low dose used here, is not effective in the treatment of photodermatosis in EPP.
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PMID:Protoporphyrin photosensitivity cannot be attenuated by oral N-acetylcysteine. 134 25

Protoporphyria is generally an autosomal dominant disease that is characterized clinically by photosensitivity and hepatobiliary disease and that is characterized biochemically by elevated protoporphyrin levels. The enzymatic activity of ferrochelatase, which catalyzes the last step in the heme biosynthetic pathway, is deficient in all tissues of patients with protoporphyria. In this study, sequencing of ferrochelatase cDNAs from a patient with protoporphyria revealed a single point mutation in the cDNAs resulting in the conversion of a Phe(TTC) to a Ser(TCC) in the carboxy-terminal end of the protein, F417S. Further, the human ferrochelatase gene was mapped to chromosome 18q21.3 by chromosomal in situ suppression hybridization. Finally, expression of recombinant ferrochelatase in Escherichia coli demonstrated a marked deficiency in activity of the mutant ferrochelatase protein and of mouse-human mutant ferrochelatase chimeric proteins. Therefore, a point mutation in the coding region of the ferrochelatase gene is the genetic defect in some patients with protoporphyria.
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PMID:A molecular defect in human protoporphyria. 137 18

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients.
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PMID:Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia. 151 89

Mutations in the visA gene of Escherichia coli cause the mutant bacteria to die upon illumination with visible light. We confirmed genetically that the visA gene is a structural gene for ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1). Since other mutations in the genes involved in the biosynthesis of heme can cure the photosensitivity, the light-induced cell death appears to be brought about by the accumulation of protoporphyrin IX, one of the substrates of ferrochelatase. When cells are illuminated with visible light, protoporphyrin IX seems to produce an active species of oxygen (probably 1O2) that is harmful to the cells. This defect is the same as that associated with the human disease protoporphyria.
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PMID:Photosensitivity of a protoporphyrin-accumulating, light-sensitive mutant (visA) of Escherichia coli K-12. 183 90

A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form.
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PMID:Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease. 193 58

Erythropoietic protoporphyria (EPP), a recently described form of porphyria, often remains unrecognized. We report the case of a 7-year-old girl admitted for investigation of photosensitivity since the age of 18 months without any significant objective cutaneous lesions. Clinical features, quantitative determinations of porphyrins in blood, urine and stools, ferrochelatase activity and cutaneous histopathology helped to confirm the diagnosis of EPP. A familial study was also performed. The clinical, laboratory and genetic characteristics of EPP are reviewed.
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PMID:Erythropoietic protoporphyria in a child. 274 12

Erythropoietic protoporphyria, caused by an inherited deficiency of ferrochelatase, results in increased free protoporphyrin concentrations in erythrocytes and plasma. Cutaneous photosensitivity is the primary clinical manifestation, but in some patients, protoporphyrin accumulation in the liver may lead to fatal hepatic failure. No treatment exists for this lethal complication. We report the case of a patient with erythropoietic protoporphyria and abnormal results of liver function tests in whom oral iron therapy led to a substantial decrease in free erythrocyte and stool protoporphyrin levels with return of liver function to normal. Iron therapy should be considered for preventing potentially fatal hepatic failure in patients with erythropoietic protoporphyria.
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PMID:Iron therapy for hepatic dysfunction in erythropoietic protoporphyria. 371 7

The ferrochelatase deficiency in protoporphyria leads to accumulation of protoporphyrin in erythrocytes and liver. Consequences are protoporphyrinemia with photosensitivity and liver damage (fibrosis, cirrhosis) with cholestasis. The latter are unpredictable and can be observed in about 10% of the patients. Protoporphyrin, the physiological main component of hepatocellular porphyrins, has a hepatotoxic effect in the high-concentrated crystalline storage form. The obligatory hepatobiliary excretion of the lipophil, erythropoietic increased accumulating protoporphyrin in protoporphyria strains the excretory function of the liver. Its restriction is followed by an exzessive protoporphyrin accumulation, which leads to protoporphyrin-induced, progressive cholestatic cirrhosis, icterus, and aggravation of the extrahepatic protoporphyrinemic cutaneous manifestation. In case of hepatobiliary complications a coproporphyria of diagnostic relevance develops with inversion of isomers. Simultaneously, the fecal protoporphyrin excretion decreases. After liver transplantation hyperbilirubinemia, protoporphyrinemia and coproporphyrinuria significantly went down. A protoporphyrinemia of about 20% of preoperative values reflects the persisting hereditary enzyme defect and the continuity of the metabolic disease.
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PMID:[Cholestatic erythrohepatic protoporphyria: porphyrin metabolism before and after liver transplantation]. 748 27


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