Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients

Abstract

BACKGROUND Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients

Experience in management of porphyria cutanea tarda in a tertiary referral Brazilian hospital from 2002 to 2017

“…Prevalence of PCT in Brazil is unknown. In most of the published PCT series, the mean age of presentation of the disease was above 40 years, and men were more affected than women, similar to our results …”

“…The known acquired precipitating factors, which induce PCT in all of PCT types, are alcoholism, hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection, and estrogen intake. Hereditary hemochromatosis (HH) is considered an inherited factor that may predispose PCT . Iron promotes the formation of reactive oxygen species (ROS) which oxidizes uroporphyrinogen, the UROD substrate, generating URO and uroporphomethene; the latter inhibits UROD because of its ability to adapt to the catalytic site of the enzyme .…”

Porphyria Cutanea Tarda (PCT) experience in Victoria, Australia

“…15 However, in our study, there was no significant association demonstrated between alcohol consumption and HFE mutation. This is similar to outcome reported by Vieiria et al 16 In a study by Lauret et 19 however, the reverse was not true. 20 HCV prevalence also varies significantly by geographic distribution with the lowest prevalence observed in Australia to be 25 per cent of PCT patients.…”

Lesões bolhosas numa mulher de pele bronzeada

“…A presença destas mutações no gene HFE tem sido largamente estudada nos doentes com PCT que apresentam uma elevada frequência da mutação C282Y em homozigotia (entre 11 e 47% nos estudos realizados na maioria dos países da Europa e EUA) 3,4,12,13 . Um estudo no norte da Itália demonstrou também uma incidência significativamente aumentada da mutação H63D nos doentes com PCT 3,4,13,14 .…”

“…Um estudo no norte da Itália demonstrou também uma incidência significativamente aumentada da mutação H63D nos doentes com PCT 3,4,13,14 . O estudo destas mutações nos doentes com PCT para além de estar indicado para rastreio genético de hemocromatose hereditária, tem também implicações no tratamento desta doença.…”