HYPERFERRITINEMIA IN THE ABSENCE OF IRON OVERLOAD

Background-Serum ferritin is normally a marker of iron overload. Ferri tin genes are sited at chromosomes 19 and 11. Regulation of ferritin s ynthesis involves an interaction between an iron regulatory protein (I RP) and part of the ferritin mRNA designated the iron regulatory eleme nt (IRE). A disorder of ferritin synthesis resulting in hyperferritina emia in the absence of iron overload has been described recently. Pati ents and methods-Hyperferritinaemia in the absence of iron overload wa s detected in a patient who was investigated for possible haemochromat osis. Serum iron, transferrin saturation, and ferritin concentration w ere studied in II members of this patient's family fi om three generat ions, Eight members had DNA samples analysed by direct cycle sequencin g of the 5' untranslated region of the E ferritin gene. Results-Six of the family members studied had serum ferritin concentrations greater than 900 mu g/l. However, serum iron and transferrin saturation were n ormal in these subjects who all had evidence of cataracts, Three affec ted family members who had genetic studies of the L ferritin gene on c hromosome 19 had an A to G point mentation which was not found in unaf fected members. Conclusions-There was complete concordance between a m utated IRE, cataracts, and hyperferritinaemia in three generations of this family. This family study confirms the finding that hereditary hy perferritinaemia in the absence of iron overload is am autosomal domin ant inherited disorder.