RESUMO
AIP is an acute liver disorder caused by a deficiency of porphobilinogen deaminase (PBGD) characterized by neuroabdominal symptoms. It is an autosomal dominant disease. However, homozygous dominant AIP (HD-AIP) have been described. In some cases erythrodontia was observed. CEP is an autosomal recessive disease produced by mutations in the uroporphyrinogen III synthase gene (UROS), characterized by severe cutaneous lesions and erythrodontia. The aim of the work was to establish the differential diagnosis of porphyria in a patient with abdominal pain, neurological attacks, skin symptoms and erythrodontia. The PBGD activity was reduced 50% and the genetic analysis indicated the presence of two genetic variants in the PBGD gene, p.G111R and p.E258G, a new genetic variant, revealing a case of heteroallelic HD-AIP. The patient, first diagnosed as a carrier of a dual porphyria: AIP / CEP based on the excretion profile of porphyrins, precursors and her clinical symptoms, would be an atypical case of human HD-AIP. These results would also suggest the presence of a phenocopy of the CEP, induced by an endogenous or exogenous factor. Our findings highlight the importance of genetic studies for a proper diagnosis of porphyria, prevention of its manifestation and its treatment.
Assuntos
Variação Genética , Hidroximetilbilano Sintase/genética , Fígado/patologia , Porfiria Aguda Intermitente/diagnóstico , Porfiria Aguda Intermitente/genética , Doença Aguda , Adulto , Sequência de Bases , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Hidroximetilbilano Sintase/metabolismo , Fígado/metabolismo , Dados de Sequência Molecular , Mutação , Porfiria Aguda Intermitente/sangue , Porfiria Aguda Intermitente/urina , Porfirinas/sangue , Porfirinas/urina , Uroporfirinogênio III Sintetase/genética , Uroporfirinogênio III Sintetase/metabolismoRESUMO
PURPOSE OF WORK: To clone, express and characterize uroporphyrinogen III synthase/methyltransferase gene (cobA/hemD) from Lactobacillus reuteri. Some strains of Lb. reuteri produce cobalamin (vitamin B(12)). Cobalamin biosynthesis relies on the sequential action of more than 25 enzymes in a complex metabolic pathway. We have cloned, expressed and characterized the gene in Lb. reuteri that codes for the S-adenosy L: -methionine uroprophyrinogen III methyltransferase/synthase (CobA/HemD), a key bifunctional enzyme in the biosynthesis of cobalamin and other tetrapyrrols.