A novel mutation of transferrin receptor 2 in a Taiwanese woman with type 3 hemochromatosis

Hereditary hemochromatosis (HH) is very rare in Asia. Here, we describe a Taiwanese woman presenting with fully developed characteristics of HH including bronze skin, DM, decreased MRI T2 signal intensity over liver and pituitary gland. Biochemistry of iron profile indicated a severe status of iron overload by serum iron: 194 μg/dL, serum ferritin: 6640 μg/L, transferrin saturation: 92.8%. By measuring the hepatic iron index 8.48 (>1.9) of her liver biopsy tissue, the diagnosis of HH was established.Diagnosis of non-HFE HH was carried out since the whole HFE genome was sequenced but failed to localize any genetic alterations. The whole genome of transferrin receptor 2 (TfR2) was sequenced and a novel mutation of 13528 G → A (Arg 481 His) in exon 11 was detected. Therefore, type 3 hemochromatosis was confirmed. The distinct clinical features, extremely high iron index and impressive iron staining in her liver biopsy tissue may represent an aggravated iron deposition in the liver caused by this novel mutation. Our finding implicates functional importance of histidine in exchange of arginine at amino acid 481 of transferrin receptor 2 in iron homeostasis.This case reminds physicians in Asia to keep in mind that hemochromatosis could be a rare cause of DM.