A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron.

Mutations of hepcidin are a rare cause of juvenile hemochromatosis (JH). We report a homozygous -25G>A mutation in the hepcidin 5' untranslated region (UTR) that generates a new start codon with a consequent frameshift. In this patient with a rare coincidental association of JH, Turner syndrome, and absolute lymphopenia, the absence of normal hepcidin synthesis was expected. Surprisingly, the patient had detectable hepcidin, suggesting that the start of translation was maintained at the original ATG with some normal protein production. However, hepcidin was not appropriately induced by an iron challenge test, supporting role of hepcidin on the clinical expression of iron overload in this case.