Successful treatment of severe hepatic impairment in erythropoietic protoporphyria:A case report and review of literature

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.

Liver disease and erythropoietic protoporphyria:A concise review

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.

Letter to the editor: Diagnosis of erythropoietic protoporphyria with severe liver injury-a case report

Erythropoietic protoporphyria(EPP)is an extremely rare disease which is often unrecognized as diagnosis.In the recent article Lui et al describe a patient with a new diagnosis of EPP with severe liver injury.Approximately 5%-20%of patients with EPP develop liver manifestations.The most severe complication of EPP is an hepatic crisis,which is a medical emergency requiring urgent treatment.Intensive treatment should consist of(exchange)transfusions and preferably in a center that performs liver transplantations.

Diagnosis of erythropoietic protoporphyria with severe liver injury: A case report

BACKGROUND Porphyria is a rare disease with complex classification. Erythropoietic protoporphyria(EPP) is an autosomal recessively inherited disease, and most are caused by mutations in the FECH gene. EPP combined with liver injury is even rarer.CASE SUMMARY This paper reports a case of EPP which was admitted to the hospital with abnormal liver function and diagnosed by repeated questioning of medical history, screening of common causes of severe liver injury, and second generation sequencing of the whole exon genome. We also summarize the clinical characteristics of EPP with liver injury, and put forward some suggestions on EPP to provide a reference for the diagnosis of such rare disease.CONCLUSION A new mutation locus(c.32_35 dupCCCT) which may be related to the disease was found by detecting the FECH gene in the pedigree of this case.

Erythropoietic Protoporphyria (A Light, Polarization and Electron Microscopical Study of the Liver in One Patient)

Objective\ To explore the hepatic pathology of a patient with erythropoietic protoporphyria (EPP). Methods\ Percutaneous liver biopsy was performed with a Chiba needle in a 31 year old man suffering from EPP. The sample was fixed in 10% formalin solution, and the paraffin embedded section was stained with H E, PAS, etc. Unstained paraffin embedded and H E stained paraffin embedded sections were examined under polarization microscope. Ultrathin sections were examined in a transmission electron microscope. Results\ In H E stained sections, deposits of dark reddish brown pigment were seen in the hepatocytes, Kupffer cells, portal macrophages and plugs in the lumen of bile canaliculi and ducts. Under light microscope, such deposits, with rare exception, exhibited striking birefringence with the unique shape of 'Maltese cross'. Non membrane limited compact masses of crystals were straight or slightly curved and their dimensions (40 640 nm in length and 6 22 nm in width) were different under the transmission electron microscope. Conclusion\ Microscopy, especially polarization microscopy, provides a highly sensitive and specific technique for the diagnosis of EPP.

Two Novel Mutations in FECH in a Patient With Erythropoietic Protoporphyria:A Case Report

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.

A rare autosomal recessive condition,congenital erythropoietic porphyria,found in the canefield rat Rattus sordidus Gould 1858

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive condition that has been reported in humansand in some animals, in which uroporphyrin 1 is deposited in the bones, teeth and urine, resulting in pink colorationand fluorescence of the tissues and urine under long-wave ultraviolet (UV) light. We observed red teeth in nine of450 canefield rats (Rattus sordidus) captured in a small, isolated patch of sugarcane in Tully, north Queensland,Australia. The skeletons of these animals were excised and were found to be bright red under normal day light.Under UV light, the skeleton had a bright red fluorescence. It is plausible that the canefield rat population in thisisolated patch of sugarcane is small and inbreeding might have occurred, resulting in incidences of the autosomalrecessive genes that cause CEP. The canefield rat can be used as an animal model for research into porphyria.

Diagnosis and treatment of icteric hepatitis caused by erythropoietic protoporphyria:A case report

Erythropoietic protoporphyria(EPP)is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase(FECH),resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissues.Here,we report a patient with photosensitive dermatitis and acute icteric hepatitis caused by EPP,whose clinical and biochemical results successfully improved following 2-month treatment with glucose load,ursodeoxycholic acid capsules,and cholestyramine powder.This case provides a reference for a combination therapy strategy for patients with liver and skin injury caused by EPP.

Liver transplantation for acute intermittent porphyria:a viable treatment?

BACKGROUND:Acute intermittent porphyria (AIP) is the most common hepatic porphyria.Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms.These symptoms result from the overproduction and accumulation of porphyrin precursors,5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG).The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred.Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks.METHOD:Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database.RESULT:LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks.CONCLUSION:LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.