title: A novel mutation of transferrin receptor 2 in a Taiwanese woman with type 3 hemochromatosis.
abstract: 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 microg/dL, serum ferritin: 6640 microg/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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medical, Kaohsiung Medical University, Taiwan, ROC.
authors.forename: Pi-Jung
authors.initials: PJ
authors.lastname: Hsiao
authors.forename: Kun-Bow
authors.initials: KB
authors.lastname: Tsai
authors.forename: Shyi-Jang
authors.initials: SJ
authors.lastname: Shin
authors.forename: Chiao-Lin
authors.initials: CL
authors.lastname: Wang
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Lee
authors.forename: Jong-Feng
authors.initials: JF
authors.lastname: Lee
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
mesh_terms: D000225:Adenine; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D003920:Diabetes Mellitus / Q000209:etiology; D005260:Female; D006147:Guanine; D006432:Hemochromatosis / Q000145:classification* / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006485:Hemosiderin / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010902:Pituitary Gland / Q000473:pathology; D017354:Point Mutation; D011990:Receptors, Transferrin / Q000235:genetics*; D013624:Taiwan
chemical_list: D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D006147:Guanine; D006485:Hemosiderin; D007501:Iron; D000225:Adenine