Características clínicas y evolutivas de una familia con hemocromatosis hereditaria tipo 1

Abstract

Introduction Hereditary hemochromatosis (HH) type I is due to mutations in the HFE gene, located on chromosome 6 (6p21.3). This disease is characterized by increased intestinal iron absorption and progressive storage in the liver, skin, pancreas, bones, heart and endocrine organs. Patient prognosis depends on early diagnosis and prompt treatment of the disease. Patients and methods We reviewed the medical records of family members (eight men and five women) with HH type I, studied and followed-up between 1985 and 2008 in Hospital Donostia, San Sebastian (Spain). Molecular studies were performed of the HFE gene and of iron overload parameters in all the family members (N = 17) belonging to two generations. In family members with the C282Y/H63D mutation and incomplete phenotype, liver iron quantification and monitoring was done by magnetic resonance imaging (MRI). Results The homozygous C282Y mutation was present in three family members, the heterozygous mutation (associated with H63D) in three, and the heterozygous mutation alone in six. Liver biopsy revealed fibrosis and / or cirrhosis in four family members (three with C282Y/C282Y and another with C282Y/-) aged over 40 years with hepatomegaly, arthralgia, and in some cases, skin pigmentation, fatigue, and hypogonadism. Liver MRI in two family members with the heterozygous mutation (C282Y/H63D) and transferrin saturation greater than 50% showed no iron overload after several years of monitoring, avoiding the need for phlebotomy. Conclusions We present the clinical manifestations of HH type 1 in this family and the molecular alterations found. Liver MRI should be incorporated into the monitoring of individuals with impaired iron metabolism and HFE gene mutations.