The metabolic signature of this disorder is the extreme hypermanganesemia with polycythemia and depleted iron stores (e.g., low ferritin and increased total iron binding capacity), whereas laboratory findings reflecting hepatic dysfunction vary even between members of the same family.1, 3 Manganese induces erythropoietin gene expression and this could be the mechanism leading to polycythemia.4 The depleted iron stores can be explained by the fact that hypermanganesemia favors the release of iron from intracellular stores, enhances iron uptake, and decreases iron utilization.5–8. The gene discussed is EPO; the disease is polycythemia.