The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of heme.In erythropoietic protoporphyria(EPP),in the majority of cases an autosom...The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of heme.In erythropoietic protoporphyria(EPP),in the majority of cases an autosomal dominant disease,there is a mutation of the gene that encodes ferrochelatase(FECH).FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes,plasma,skin and liver.The prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 000.Clinical manifestations of EPP appear in early infancy upon first exposure to the sun.Nevertheless,approximately 5%-20% of patients with EPP develop liver manifestations.Retention of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity,such as cholelithiasis,mild parenchymal liver disease,progressive hepatocellular disease with end-stage liver disease and acute liver failure.Liver damage is the major risk in EPP patients,so surveillance and frequent clinical and biochemical liver follow-up is mandatory.The diagnostic approach consists in detecting increased levels of protoporphyrin,decreased activity of FECH and genetic analysis of the FECH gene.A variety of nonsurgical therapeutic approaches have been adopted for the management of EPP associated with liver disease,but none of these has been shown to be unequivocally efficacious.Nevertheless,some may have a place in preparing patients for liver transplantation.Liver transplantation does not correct the constitutional deficiency of FECH.Consequently,there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of protoporphyrin.Some authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.展开更多
BACKGROUND Erythropoietic protoporphyria(EPP)is a rare genetic disorder stemming from ferrochelatase gene mutations,which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes,skin,bone marrow ...BACKGROUND Erythropoietic protoporphyria(EPP)is a rare genetic disorder stemming from ferrochelatase gene mutations,which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes,skin,bone marrow and liver.Although porphyria-related severe liver damage is rare,its consequences can be severe with limited treatment options.CASE SUMMARY This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment,employing a combination of red blood cell(RBC)exchange and therapeutic plasma exchange(TPE).The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange.CONCLUSION The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.展开更多
Erythropoietic protoporphyria（EPP）, an autosomal dominant disease, is caused by partial deficiency of ferrochelatase（FECH）, which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutati...Erythropoietic protoporphyria（EPP）, an autosomal dominant disease, is caused by partial deficiency of ferrochelatase（FECH）, which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630–634 nm, and analysis of FECH gene mutations. Using gene scanning, we identified a small deletion in the FECH gene（c.973 delA） in one proband（patient A） and a pathogenic FECH mutation（c.1232 GT） in the other（patient B） and also observed some nucleotide variations（c.798 CG, c.921 AG, IVS1-23 CT, IVS3＋23 AG, IVS9＋35 CT, and IVS3-48 TC） in these patients. The family pedigree of patient A was then established by characterization of the genotype of the patient＇s relatives. We also analyzed the potential perniciousness of the missense mutation with bioinformatic software, Polyphen and Sift. In summary, Chinese EPP patients have similar manifestations to those of Caucasians, and identification of the Chinese FECH gene mutations expands the FECH genotypic spectrum and may contribute to genetic counseling.展开更多
Introduction:Erythropoietic protoporphyria(EPP)is a rare photodermatosis mainly caused by deficiency of the enzyme ferrochelatase(FECH).We herein report a case of EPP associated with 2 novel mutations in FECH.Case pre...Introduction:Erythropoietic protoporphyria(EPP)is a rare photodermatosis mainly caused by deficiency of the enzyme ferrochelatase(FECH).We herein report a case of EPP associated with 2 novel mutations in FECH.Case presentation:A 15-year-old boy experienced pain and pruritus after sunlight exposure.He had occasional claret-red urine,hepatomegaly with increased alanine aminotransferase and aspartate aminotransferase levels,and an elevated free erythrocyte protoporphyrin level.He was treated with oralβ-carotene and cholestyramine and avoidance of sunlight as much as possible.Discussion:Genome sequencing revealed 2 novel FECH mutations that had been inherited from his healthy parents.Pathogenicity analysis involving prediction using PolyPhen-2,SIFT,and Mutation Taster revealed that the 2 novel mutations were likely pathogenic.Although the patient’s parents were healthy,they each had one of these 2 mutations.This finding is consistent with previous reports stating that individuals carrying low-expression alleles can be asymptomatic.The pathogenesis of the disease caused by these 2 mutations requires verification by larger and more detailed studies.Conclusion:Although the precise role of these mutations in EPP is not clear,the findings in the present case expand the genotypic spectrum of the disease.展开更多
文摘The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of heme.In erythropoietic protoporphyria(EPP),in the majority of cases an autosomal dominant disease,there is a mutation of the gene that encodes ferrochelatase(FECH).FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes,plasma,skin and liver.The prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 000.Clinical manifestations of EPP appear in early infancy upon first exposure to the sun.Nevertheless,approximately 5%-20% of patients with EPP develop liver manifestations.Retention of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity,such as cholelithiasis,mild parenchymal liver disease,progressive hepatocellular disease with end-stage liver disease and acute liver failure.Liver damage is the major risk in EPP patients,so surveillance and frequent clinical and biochemical liver follow-up is mandatory.The diagnostic approach consists in detecting increased levels of protoporphyrin,decreased activity of FECH and genetic analysis of the FECH gene.A variety of nonsurgical therapeutic approaches have been adopted for the management of EPP associated with liver disease,but none of these has been shown to be unequivocally efficacious.Nevertheless,some may have a place in preparing patients for liver transplantation.Liver transplantation does not correct the constitutional deficiency of FECH.Consequently,there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of protoporphyrin.Some authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.
文摘BACKGROUND Erythropoietic protoporphyria(EPP)is a rare genetic disorder stemming from ferrochelatase gene mutations,which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes,skin,bone marrow and liver.Although porphyria-related severe liver damage is rare,its consequences can be severe with limited treatment options.CASE SUMMARY This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment,employing a combination of red blood cell(RBC)exchange and therapeutic plasma exchange(TPE).The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange.CONCLUSION The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.
基金supported by the National Basic Research Project(973)of China(No.2012CB934000)the National Distinguished Youth Scholar Grant of China(No.31325010)
文摘Erythropoietic protoporphyria（EPP）, an autosomal dominant disease, is caused by partial deficiency of ferrochelatase（FECH）, which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630–634 nm, and analysis of FECH gene mutations. Using gene scanning, we identified a small deletion in the FECH gene（c.973 delA） in one proband（patient A） and a pathogenic FECH mutation（c.1232 GT） in the other（patient B） and also observed some nucleotide variations（c.798 CG, c.921 AG, IVS1-23 CT, IVS3＋23 AG, IVS9＋35 CT, and IVS3-48 TC） in these patients. The family pedigree of patient A was then established by characterization of the genotype of the patient＇s relatives. We also analyzed the potential perniciousness of the missense mutation with bioinformatic software, Polyphen and Sift. In summary, Chinese EPP patients have similar manifestations to those of Caucasians, and identification of the Chinese FECH gene mutations expands the FECH genotypic spectrum and may contribute to genetic counseling.
文摘Introduction:Erythropoietic protoporphyria(EPP)is a rare photodermatosis mainly caused by deficiency of the enzyme ferrochelatase(FECH).We herein report a case of EPP associated with 2 novel mutations in FECH.Case presentation:A 15-year-old boy experienced pain and pruritus after sunlight exposure.He had occasional claret-red urine,hepatomegaly with increased alanine aminotransferase and aspartate aminotransferase levels,and an elevated free erythrocyte protoporphyrin level.He was treated with oralβ-carotene and cholestyramine and avoidance of sunlight as much as possible.Discussion:Genome sequencing revealed 2 novel FECH mutations that had been inherited from his healthy parents.Pathogenicity analysis involving prediction using PolyPhen-2,SIFT,and Mutation Taster revealed that the 2 novel mutations were likely pathogenic.Although the patient’s parents were healthy,they each had one of these 2 mutations.This finding is consistent with previous reports stating that individuals carrying low-expression alleles can be asymptomatic.The pathogenesis of the disease caused by these 2 mutations requires verification by larger and more detailed studies.Conclusion:Although the precise role of these mutations in EPP is not clear,the findings in the present case expand the genotypic spectrum of the disease.
