Porphyria cutanea tarda with C282Y and H63D hemochromatosis gene mutations and retrospective analysis of the iron profile regarding the treatment: study of 50 cases

• Grant number: 10/51781-4
• Support type: Regular Research Grants
• Duration: October 01, 2010 - September 30, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Vitor Manoel Silva dos Reis
• Grantee: Vitor Manoel Silva dos Reis
• Home Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Porphyria cutanea tarda (PCT) is characterized by a deficient activity of the uroporphyrinogen decarboxilase (UROD) and accumulation of uroporphyrin. Acquired PCT has precipitating factors: ethanol, viral infections (hepatitis B, hepatitis C and human immunodeficiency viruses (HIV)), estrogen and chronic kidney disease. PCT has been associated with: diabetes mellitus, lupus erythematosus, hepatocellular carcinoma, hematologic neoplasm and hemochromatosis. Hereditary hemochromatosis (HHC) is an autosomal recessive genetic disorder, which symptoms occur after the third decade of life, as the deposition of iron is gradual and cumulative mainly in the liver, pancreas, heart, joints and pituitary gland. Two mutations on the HFE gene (C282Y and H63D) are significantly correlated with HHC. Clinical manifestations are more expressive in patients with the C282Y mutation. Various reports describe an increase in the frequency of mutations on the HFE gene in patients with PCT. PCT normally presents iron overload, therefore the iron levels and ferritin can't be used as a sign for HHC in these cases. In addition, ferritin may be increased in viral infections associated to PCT. PCT treatment is phlebotomy and/or low doses of oral chloroquine phosphate. The objective of this study is: 1. Identify the C282Y and H63D mutations on the FIFE gene in patients with PCT, because the diagnosis of HHC and its early treatment prevent the disease progression; 2. Identify the association with ethanol, hepatitis C, hepatitis B and HIV infection and do the correlation with the presence or absence of the mutations; and 3. Study retrospectively the therapeutical response of the patients, with or without mutations, treated with chloroquine. The study can contribute for PCT to become a cutaneous marker for the diagnosis of HHC, permitting an early treatment and preventing complications. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

JORGE VIEIRA, FATIMA MENDONCA; NAKHLE, MARIA CRISTINA; ABRANTES-LEMOS, CLARICE PIRES; RACHID CANCADO, EDUARDO LUIZ; SILVA DOS REIS, VITOR MANOEL. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients. ANAIS BRASILEIROS DE DERMATOLOGIA, v. 88, n. 4, p. 530-540, JUL-AUG 2013. Web of Science Citations: 8.