1. Molecular characterization of porphyrias in Italy: a diagnostic flow-chart.
- Author
-
Martinez di Montemuros F, Di Pierro E, Patti E, Tavazzi D, Danielli MG, Biolcati G, Rocchi E, and Cappellini MD
- Subjects
- DNA metabolism, Ferrochelatase genetics, Flavoproteins, Heme metabolism, Humans, Hydroxymethylbilane Synthase genetics, Italy, Mitochondrial Proteins, Mutation, Oxidoreductases genetics, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Porphyria Cutanea Tarda genetics, Porphyria, Acute Intermittent genetics, Porphyria, Hepatoerythropoietic genetics, Porphyrias, Hepatic genetics, Porphyrins genetics, Protoporphyrinogen Oxidase, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, Sensitivity and Specificity, Spectrometry, Fluorescence, Uroporphyrinogen Decarboxylase genetics, Oxidoreductases Acting on CH-CH Group Donors, Porphyrias diagnosis, Porphyrias genetics
- 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.
- Published
- 2002