Liver disease and erythropoietic protoporphyria: a concise review (original) (raw)
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New insights into the pathogenesis of erythropoietic protoporphyria and their impact on patient care
European Journal of Pediatrics, 2000
Erythropoietic protoporphyria (EPP, MIM 177000) is an inherited disorder caused by a partial de®ciency of ferrochelatase (FECH) which catalyses the chelation of iron into protoporphyrin to form haem. The majority of EPP patients experience solely a painful photosensitivity whereas a small number of them develop liver complications due to the accumulation of excessive amount of protoporphyrin in the liver. EPP is considered to be an autosomal dominant disorder, however, with a low clinical penetrance. To date, a total of 65 dierent mutations have been identi®ed in the FECH gene of EPP patients. Among the 89 EPP patients who carry a``null allele'' mutation which results in the formation of a truncated protein, 18 of them developed EPP-related liver complications.
Journal of Clinical Investigation, 1991
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 unfrequent in the human, this mutation may represent a model for the human disease, especially in its severe form.
AJP: Gastrointestinal and Liver Physiology, 2005
5 other HighWire hosted articles This article has been cited by [PDF] [Full Text] [Abstract] , January 15, 2007; 109 (2): 811-818. Blood anemia in ferrochelatase-deficient mice Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic [PDF] [Full Text] , July , 2007; 56 (7): 1009-1018. Gut A V Anstey and R J Hift Liver disease in erythropoietic protoporphyria: insights and implications for management [PDF] [Full Text] [Abstract] , Clinical, Biochemical, and Genetic Study of 11 Patients With Erythropoietic [PDF] [Full Text] [Abstract] , December 1, 2007; 110 (12): 4108-4110. Blood Badminton S. Alexander Holme, Mark Worwood, Alexander V. Anstey, George H. Elder and Michael N. Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria [PDF] [Full Text] , December , 2007; 83 (986): 739-748. Postgrad Med J
Molecular medicine (Cambridge, Mass.)
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 c...
Identification of a ferrochelatase mutation in a Chinese family with erythropoietic protoporphyria
Journal of Hepatology, 2008
Background/Aims: Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of heme biosynthesis characterized by a partial decrease in ferrochelatase (FECH) activity leading to excessive accumulation of protoporphyrin. While a majority of EPP patients only exhibit photosensitivity, a small percentage of patients also develop liver complications and need liver transplantation. Methods: In this study, we have sequenced the ferrochelatase gene of a Chinese EPP patient who suffered from EPPrelated liver complications. Results: A nonsense mutation in exon 4, 343C>T, introducing a premature stop codon at position arginine 115, was identified in the proband as well as her symptomatic mother and brother, but was absent in her father. All the family members with overt photosensitivity also carried the low-expressed allele IVS3-48c, whose prevalence in the Chinese Han population was determined to be 41.35% and which was also functional in producing an aberrant 63 bp insertion. Conclusions: We describe the first FECH mutation identified in the Chinese Han population and report a high frequency of the hypomorphic IVS3-48c allele in China.
Molecular Genetics and Metabolism Reports, 2019
Erythropoietic protoporphyria (EPP) is an autosomal recessive deficiency in heme biosynthesis due to pathogenic variants in the ferrochelatase gene (FECH). Patients present with lifelong photosensitivity and potential liver disease. Here we report a novel FECH variant designated c.904_912+1del found in trans with the c.315-48T > C hypomorphic variant, in one family with three affected individuals. These patients presented with immediate painful cutaneous photosensitivity but no hepatic manifestations. All have elevated protoporphyrin levels consistent with a diagnosis of EPP. Genetic, biochemical, and functional assay results obtained for this family suggest that the unique variant c.904_912+1del is likely pathogenic and thus causative of EPP.
Erythropoietic protoporphyria and early onset of cholestasis
The Turkish journal of pediatrics
Erythropoietic protoporphyria (EPP) is an inherited defect of mitochondrial ferrochelatase. This defect results in accumulation of protoporphyrin in erythrocytes, plasma, liver, and skin, which causes severe photosensitivity. Liver disease can occur in 1-4% of the patients with EPP, usually after at least a decade of photosensitivity. Herein, we describe a 1.5-year-old child with EPP with severe photosensitivity, heart abnormalities and early onset of cholestatic liver disease, whose clinical condition improved gradually after using ursodeoxycholic acid. It seems that liver disease in EPP patients is not limited to the late phases of the disease and could develop in childhood and early phases of EPP. Awareness among physicians has a major role in the early detection and prevention of mistreatment of EPP in case of its combination with other abnormalities.
Mutations in the Ferrochelatase Gene of Four Spanish Patients with Erythropoietic Protoporphyria
Journal of Investigative Dermatology, 1998
Erythropoietic protoporphyria is a hereditary disorder of porphyrin metabolism caused by mutations in the ferrochelatase gene. Ferrochelatase catalyzes the chelation of ferrous iron into protoporphyrin IX to form heme. Mutation analysis was performed in four Spanish erythropoietic protoporphyria families resulting in the identification of four different mutations in the ferrochelatase gene. Two of them were novel mutations, a missense mutation (1157 A→C, H386P) and a frameshift mutation (843delC) found in two Spanish families, respectively. The third and the forth Spanish patients carried already published ferrochelatase gene mutations, a nonsense mutation (343C→T, R115X) and a missense mutation (557T→C, I186T),