Two Cases Of Porphyrias Caused By Mutation Of Genes Of Hemoglobin Synthesis-related Enzymes And Literatures Review

BackgroundPorphyria is a syndrome of abnormal porphyrin metabolism,which is caused by specific enzyme defects in the process of heme biosynthesis.Heme is involved in the composition of hemoglobin and exists in all tissues in the body.The biosynthesis of heme can be divided into 8 steps,in which 8 different enzymes(ALA synthase.ALA dehydratase,PBG deaminase,uroporphyrinogen Ⅲ polymerization,uroporphyrinogen decarboxylase,coproporphyrinogen oxidase,protoporphyrinogen oxidase and ferrochelatase)play important roles.The activity of enzyme will change when there are mutation or mutations on certain sites of gene of specific enzyme in the process,which leading to the disordered porphyrin metabolism,the mutation of different enzymes will cause different types of porphyria.Porphyrias can be classified as hepatic and erythropoietic porphyrias due to the heme precursors such as 5-aminolevulinic acid(ALA),porphobilinogen and porphyrins being overproduced and deposited in certain systems.Hepatic porphyrias include acute porphyrias and chronic hepatic porphyrias.The acute porphyrias include acute intermittent porphyria(AIP),hereditary coproporphyria(HCP),variegate porphyria(VP)and δ-aminolevulinic acid dehydratase porphy-ria(ADP).Chronic hepatic porphyrias include porphyria cutanea tarda(PCT)and hepatoerythropoietic porphyria(HEP).The erythropoietic porphyrias includecongenital erythropoietic porphyria(EPP),X-Linked sideroblastic anemia(XLSA)and congenital erythropoietic porphyria(CEP).This article summarizes and analyzes the clinical features,laboratory examinations,genetic testing,etc.of erythropoietic protoporphyria(EPP)caused by the mutation of FECH gene and hepatoerythropoietic porphyria(HEP)caused by the mutation of UROD gene,to help clinicians have a better understanding of porphyria,thereby reducing misdiagnosis and improving the quality of life of patients as much as possible.ObjectiveTo explore and summarize the clinical characteristics,pathogenesis,laboratory examination characteristics,gene mutation sites,treatments of EPP and HEP.Methods1.Reported 1 case of erythropoietic protoporphyria and 1 case of hepatoerythropoietic porphyria diagnosed and treated in our department respectively;2.Searched on "Chinese National Knowledge Infrastructure(CNKI)","Wanfang Database","Weipu network" platform with the searching terms "erythropoietic protoporphyria" and "hepatoerythropoietic porphyria" respectively;3.Used "Erythropoietic protoporphyria" and"Hepatoerythropoietic porphyria" as the searching terms to search on"PubMed","Geenmedical",and "Web of Science";4.Inclusion criteria:① Cases of erythropoietic protoporphyria and hepatoerythropoietic porphyria reported in domestic and foreign journals;② The clinical manifestations and auxiliary examinations were basically complete;③The cases diagnosed by Genetic testing;5.Elimination criteria:①Eliminate journal publication catalogs,plans,solicitation notices etc;② Eliminate the same documents in different websites;③Eliminate documents with incomplete case data;6.Selected relevant documents according to the inclusion criteria and elimination criteria;7.Collected and analyzed the clinical data of the included literature reported cases and two cases in our hospital.Results1.General information15 cases were included,10 EPP and 5 HEP.The age of clearly diagnosed of EPP ranges from 2 to 53 years old.There are 7 males and 3 females.The age of clearly diagnosed of HEP ranges from 13 months to 78 years,including 2 males and 3 females.2.Clinical manifestationsEPP:Mostly occurs in children when they are 2-5 years old,photosensitivity,erythema,swelling,pain,itching,waxy scars on the sun-exposed skin such as the back of the hands and face,the dermatoglyph of the facial skin was deepen and widen,the skin around the mouth was of radial dermatoglyph,and densely skin-colored papules could be seen on the dorsal hands.HEP:Onset in infancy,photosensitivity,erythema,blisters,pain and itching on the exposed skin;hyperpigmentation;sclerosis;hairy;scleroderma-like lesions could also be seen.3.Laboratory testingEPP:The protoporphyrin was increased in plasma,red blood cells and feces;HEP:The Zinc protoporphyrin in red blood cells,porphyrin(Ⅰ and Ⅲ)and carboxyl porphyrin in urine were increased.4.DNA TestingEPP:Detected the mutation of FECH gene;HEP:Detected the mutation of UROD gene.5.TreatmentEPP:3 cases were treated with β-carotene in combination with sun protection,2 cases were treated with cimetidine in combination with sun protection,1 case used ursodeoxycholic acid in combination with sun protection as therapy,and 5 cases were managed with sun protection alone.HEP:All 5 cases were treated with sunscreen instead of drugs.Conclusion1.There were mutations of multiple sites in FECH gene of EPP patients,we found two sites mutations on FECH gene:c.181C>T(p.Q61X)and IVS3-48C(T>C);c.181 C>T(p.Q61X)mutation was firstly reported so far as I known.2.HEP is a rare congenital porphyria caused by the decrease or lack of activity of uroporphyrinogen decarboxylase,we found a missense mutation of UROD:(c.919C>G(p.P307A)),the HGMD database does not have a correlation report of this locus,and the Clinvar database does not have the results of pathogenicity analysis of this locus.