Detection of hereditary hemochromatosis and biochemical iron overload in primary care: A multicenter case finding study in Spain

Abstract

Although the C282Y HFE gene substitution is the most common mutation among individuals from Northern Europe in Spain and Italy, this mutation has a lower prevalence and thus a lower proportion of Spanish and Italian patients are C282Y homozygotes in comparison to Northern European descendants. These differences prompted us to explore the expression of hereditary hemochromatosis (HH) in a set of Spanish individuals in primary care settings. We undertook a multicenter prospective case-finding study including 2,739 individuals. Subjects with consistent elevated transferring saturation and/or serum ferritin levels were referred has having elevated iron measures (EIM), and molecular analyses for HFE-gene were performed. EIM were consistently found in 126 subjects. Among them 14 HH patients were identified (3 C282Y homozygotes and 11 compound C282Y/H63D heterozygotes), including subjects from familial studies. A hitherto new mutation of HFE was detected (V284M/H63D) as well as a family carrying a hereditary hyperferritinemia/cataract syndrome (HHCS) with a C39T mutation in L-ferritin gene. A 5-year follow-up of patients with HH showed a steady state of the iron measurements as well as in their clinical situation. Forty-five percent of patients with EIM had metabolic syndrome. This is the first case-finding study performed in Spain on these topics.