# Iron overload is not the same everywhere: Particularities of iron-metabolism gene mutations in Brazil and a proposal for the investigation and management of iron overload in this population

## TL;DR

This paper discusses how iron overload in Brazil has unique genetic causes and proposes a new approach for diagnosing and managing it.

## Contribution

The study identifies distinct genetic mutations in Brazilian iron overload cases and proposes a tailored diagnostic algorithm for this population.

## Key findings

- HFE C282Y/C282Y mutations are less prevalent in Brazil compared to European populations.
- TFR2, SCL40A1, HJV, HAMP, BMP6, and SLC11A1 gene mutations are significant in Brazilian iron overload cases.
- A new diagnostic and management algorithm is proposed for iron overload in Brazil.

## Abstract

There is no physiological mechanism for the excretion of iron in humans, and excess iron may lead to severe tissue damage if not adequately treated. Iron overload can be caused by genetic factors (hemochromatosis) or acquired conditions (e.g., ineffective erythropoiesis, transfusions, iatrogenic iron treatment, viral hepatitis, alcohol intake, severe liver disease, metabolic dysfunction), and, in many cases, by a conjunction of these factors. Historically, guidelines for the genetic investigation of patients with iron overload have been based on data obtained from Caucasian individuals in Europe and North America. However, due to the genetic heterogeneity of iron overload gene mutations worldwide, these recommendations might not be applicable to other ethnic groups. This study analyzed previously published genetic data obtained from Brazilian patients with iron overload and found a relevant but small prevalence of HFE C282Y/C282Y patients when compared to European populations, while mutations of the TFR2, SCL40A1, HJV, HAMP, BMP6 and SLC11A1 genes seem to be important. This study proposes an adapted algorithm for the investigation and management of iron overload in Brazil.