title: Molecular characterization of porphyrias in Italy: a diagnostic flow-chart.
abstract: The porphyrias are disorders associated with inherited or acquired enzyme deficiencies in the heme biosynthetic pathway. The differential diagnosis is often difficult since the phenotype is very similar in some forms and the biochemical tests are not commonly available. Here we provide an update on the molecular diagnosis of porphyrias in Italy and a flow-chart to facilitate the identification of mutations in heme biosynthetic genes. The molecular analysis has allowed us to identify the molecular defect underlying the disease in 66 probands with different porphyrias [acute intermittent porphyria (AIP), variegate porphyria (VP), porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP)]. No Italian patients with defects in coproporphyrinogen oxidise (CPOX) gene, responsible for hereditary coproporphyria (HCP), have been detected. The molecular characterization has been extended to 115 relatives with the identification of 55 asymptomatic mutation carriers and 60 normal subjects. We have so far identified 50 different mutations among 4 genes associated with the most common porphyrias showing a high molecular heterogeneity: 22 in the hydroxymethylbilane synthase (HMBS) gene (AIP), 7 in the protoporphyrinogen oxidase (PPOX) gene (VP), 16 in the uroporphyrinogen decarboxylase (UROD) gene (PCT) and 5 in the ferrochelatase (FECH) gene (EPP). Among the 50 molecular defects, 29 seem to be restricted to the Italian population.
authors.affiliation: Dipartimento di Medicina Interna, University of Milan, Ospedale Maggiore Policlinico IRCCS, Via F. Sforza 35, 20122 Milan, Italy. franco.martinez@unimi.it
authors.forename: F
authors.initials: F
authors.lastname: Martinez di Montemuros
authors.forename: E
authors.initials: E
authors.lastname: Di Pierro
authors.forename: E
authors.initials: E
authors.lastname: Patti
authors.forename: D
authors.initials: D
authors.lastname: Tavazzi
authors.forename: M G
authors.initials: MG
authors.lastname: Danielli
authors.forename: G
authors.initials: G
authors.lastname: Biolcati
authors.forename: E
authors.initials: E
authors.lastname: Rocchi
authors.forename: M D
authors.initials: MD
authors.lastname: Cappellini
mesh_terms: D004247:DNA / Q000378:metabolism; D005294:Ferrochelatase / Q000235:genetics; D005420:Flavoproteins; D006418:Heme / Q000378:metabolism; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics; D007558:Italy; D024101:Mitochondrial Proteins; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017119:Porphyria Cutanea Tarda / Q000235:genetics; D017118:Porphyria, Acute Intermittent / Q000235:genetics; D017121:Porphyria, Hepatoerythropoietic / Q000235:genetics; D011164:Porphyrias / Q000175:diagnosis* / Q000235:genetics*; D017094:Porphyrias, Hepatic / Q000235:genetics; D011166:Porphyrins / Q000235:genetics; D050768:Protoporphyrinogen Oxidase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D014575:Uroporphyrinogen Decarboxylase / Q000235:genetics
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D011166:Porphyrins; D006418:Heme; D004247:DNA; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase; D011163:Hydroxymethylbilane Synthase; D014575:Uroporphyrinogen Decarboxylase; D005294:Ferrochelatase