title: Clinicopathological study of Japanese patients with genetic iron overload syndromes.
abstract: In addition to hemochromatosis, aceruloplasminemia and ferroportin disease may be complicated by iron-induced multiple organ damage. Therefore, clinicopathological features should be evaluated in a wider range of genetic iron disorders. This study included 16 Japanese patients with genetic iron overload syndromes. The responsible genes were CP in four, HAMP in one, HJV in three, TFR2 in five, and SLC40A1 in three patients. No phenotype dissociation was observed in patients with the CP, TFR2, or HAMP genotypes. Two of the three patients with the HJV genotype displayed classic hemochromatosis instead of the juvenile type. Patients with the SLC40A1 genotype were affected by mild iron overload (ferroportin A) or severe iron overload (ferroportin B). Transferrin saturation was unusually low in aceruloplasminemia patients. All patients, except those with ferroportin disease, displayed low serum hepcidin-25 levels. Liver pathology showed phenotype-specific changes; isolated parenchymal iron loading in aceruloplasminemia, periportal fibrosis associated with heavy iron overload in both parenchymal and Kupffer cells of ferroportin B, and parenchyma-dominant iron-loading cirrhosis in hemochromatosis. In contrast, diabetes occurred in all phenotypes of aceruloplasminemia, hemochromatosis, and ferroportin disease B. In conclusion, clinicopathological features were partially characterized in Japanese patients with genetic iron overload syndromes.
authors.affiliation: Department of Medical Technology, Nagoya University Graduate School of Health Sciences, Nagoya, Japan. ai-hat@dpc.agu.ac.jp
authors.forename: Ai
authors.initials: A
authors.lastname: Hattori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tatsumi
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics*; D002570:Ceruloplasmin / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D007564:Japan / Q000453:epidemiology; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000235:genetics*; D013577:Syndrome; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D005819:Genetic Markers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; C545475:hepcidin 25, human; D000098742:Ferroportin; D002570:Ceruloplasmin