TfR2ヘテロ接合型変異で発症したヘモクロマトーシスの1例
症例は38歳，男性．肝機能障害にて当科を受診し，血液検査で肝酵素の上昇に加え，血清鉄，フェリチンの上昇を認めた．肝生検組織の鉄染色で肝細胞に鉄沈着を認めた．輸血や鉄剤での治療の既往はなく，HFE，HJV，HAMP，TfR2，SLC40A1の鉄代謝関連遺伝子検査を行い，TfR2のヘテロ接合型変異（c.1206c＞M）を認めた．以上の結果からtype3遺伝性ヘモクロマトーシスと診断し，食生活の変更とともに定期的な瀉血療法を行ったところ，血清フェリチンは正常化し，肝機能は改善した．TfR2の変異による遺伝性ヘモクロマトーシスは常染色体劣性遺伝であり，通常はホモ接合型で発症する．本症例はTfR2のヘテ...
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| Published in | 肝臓 Vol. 63; no. 3; pp. 151 - 157 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本肝臓学会
01.03.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.63.151 |
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| Abstract | 症例は38歳，男性．肝機能障害にて当科を受診し，血液検査で肝酵素の上昇に加え，血清鉄，フェリチンの上昇を認めた．肝生検組織の鉄染色で肝細胞に鉄沈着を認めた．輸血や鉄剤での治療の既往はなく，HFE，HJV，HAMP，TfR2，SLC40A1の鉄代謝関連遺伝子検査を行い，TfR2のヘテロ接合型変異（c.1206c＞M）を認めた．以上の結果からtype3遺伝性ヘモクロマトーシスと診断し，食生活の変更とともに定期的な瀉血療法を行ったところ，血清フェリチンは正常化し，肝機能は改善した．TfR2の変異による遺伝性ヘモクロマトーシスは常染色体劣性遺伝であり，通常はホモ接合型で発症する．本症例はTfR2のヘテロ接合型変異であったが，肉類の摂取量が多く，生活習慣が発症に寄与した可能性が示唆され，瀉血療法に加えて生活習慣の変更が鉄過剰の改善に有効であった． |
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| AbstractList | 症例は38歳，男性．肝機能障害にて当科を受診し，血液検査で肝酵素の上昇に加え，血清鉄，フェリチンの上昇を認めた．肝生検組織の鉄染色で肝細胞に鉄沈着を認めた．輸血や鉄剤での治療の既往はなく，HFE，HJV，HAMP，TfR2，SLC40A1の鉄代謝関連遺伝子検査を行い，TfR2のヘテロ接合型変異（c.1206c＞M）を認めた．以上の結果からtype3遺伝性ヘモクロマトーシスと診断し，食生活の変更とともに定期的な瀉血療法を行ったところ，血清フェリチンは正常化し，肝機能は改善した．TfR2の変異による遺伝性ヘモクロマトーシスは常染色体劣性遺伝であり，通常はホモ接合型で発症する．本症例はTfR2のヘテロ接合型変異であったが，肉類の摂取量が多く，生活習慣が発症に寄与した可能性が示唆され，瀉血療法に加えて生活習慣の変更が鉄過剰の改善に有効であった． |
| Author | 森野, 加帆里 阿部, 慎太郎 生田, 克哉 原田, 大 宮川恒, 一郎 土岐, 康通 柴田, 道彦 西尾, 仁 熊元, 啓一郎 大江, 晋司 巽, 康彰 本間, 雄一 林, 久男 |
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| References | 21) Hino K, Nishina S, Hara Y. Iron metabolic disorder in chronic hepatitis C: mechanisms and relevance to hepatocarcinogenesis. J Gastroenterol Hepatol 2013; 28 Suppl 4: 93-98 1) Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet 2016; 388: 706-716 5) Hayashi H, Wakusawa S, Motonishi S, et al. Genetic background of primary iron overload syndromes in Japan. Intern Med 2006; 45: 1107-1111 16) Koyama C, Wakusawa S, Hayashi H, et al. Two novel mutations, L490R and V561X, in the transferrin receptor 2 in Japanese patients with hemochromatosis. Haematologica 2005; 90: 302-307 18) Majore S, Ricerca BM, Radio FC, et al. Type 3 hereditary hemochromatosis in a patient from sub-Saharan Africa: is there a link between African iron overload and TFR2 dysfunction? Blood Cells Mol Dis 2013; 50: 31-32 12) De Domenico I, Ward DM, Musci G, et al. Iron overload due to mutations in ferroportin. Haematologica 2006; 91: 92-95 15) Hattori A, Wakusawa S, Hayashi H, et al. AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with hemochromatosis. Hepatol Res 2003; 26: 154-156 19) Fujihara J, Yasuda T, Kimura-Kataoka K, et al. Association of SNPs in transferrin and transferrin receptor genes with blood iron levels in human. Leg Med (Tokyo) 2019; 36: 17-20 11) Hollerer I, Bachmann A, Muckenthaler MU. Pathophysiological consequences and benefits of HFE mutations: 20 years of research. Haematologica 2017; 102: 809-817 6) Hayashi H, Yano M, Urawa N, et al. A 10-year follow-up study of a Japanese family with ferroportin disease A: mild iron overload with mild hyperferritinemia co-occurring with hyperhepcidinemia may be benign. Intern Med 2018; 57: 2865-2871 13) Bardou-Jacquet E, Ben Ali Z, Beaumont-Epinette MP, et al. Non-HFE hemochromatosis: pathophysiological and diagnostic aspects. Clin Res Hepatol Gastroenterol 2014; 38: 143-154 20) Pichler I, Minelli C, Sanna S, et al. Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. Hum Mol Genet 2011; 20: 1232-1240 3) Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 2010; 139: 393-408 10) Barton JC, Edwards CQ, Acton RT. HFE gene: Structure, function, mutations, and associated iron abnormalities. Gene 2015; 574: 179-192 4) Bomford A. Genetics of haemochromatosis. Lancet 2002; 360: 1673-1681 14) 土田健一, 種田紳二, 三澤和史, 他. 糖尿病, 下垂体性腺機能低下症, 肝線維化を呈した新規TfR2遺伝子変異による原発性ヘモクロマトーシス (HH Type3) の1例. 糖尿病 2010; 53: 247-252 7) Kawabata H, Yang R, Hirama T, et al. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem 1999; 274: 20826-20832 2) Ikuta K, Hatayama M, Addo L, et al. Iron overload patients with unknown etiology from national survey in Japan. Int J Hematol 2017; 105: 353-360 9) Girelli D, Trombini P, Busti F, et al. A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis. Haematologica 2011; 96: 500-506 17) Kawaguchi T, Ikuta K, Tatsumi Y, et al. Identification of heterozygous p.T150C and p.V274M mutations in HJV gene in a Japanese patient with mild phenotype of juvenile hemochromatosis: A case report. Hepatol Res 2019; 50: 144-150 8) Radio FC, Majore S, Binni F, et al. TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy. Blood Cells Mol Dis 2014; 52: 83-87 |
| References_xml | – reference: 12) De Domenico I, Ward DM, Musci G, et al. Iron overload due to mutations in ferroportin. Haematologica 2006; 91: 92-95 – reference: 14) 土田健一, 種田紳二, 三澤和史, 他. 糖尿病, 下垂体性腺機能低下症, 肝線維化を呈した新規TfR2遺伝子変異による原発性ヘモクロマトーシス (HH Type3) の1例. 糖尿病 2010; 53: 247-252 – reference: 21) Hino K, Nishina S, Hara Y. Iron metabolic disorder in chronic hepatitis C: mechanisms and relevance to hepatocarcinogenesis. J Gastroenterol Hepatol 2013; 28 Suppl 4: 93-98 – reference: 17) Kawaguchi T, Ikuta K, Tatsumi Y, et al. Identification of heterozygous p.T150C and p.V274M mutations in HJV gene in a Japanese patient with mild phenotype of juvenile hemochromatosis: A case report. Hepatol Res 2019; 50: 144-150 – reference: 5) Hayashi H, Wakusawa S, Motonishi S, et al. Genetic background of primary iron overload syndromes in Japan. Intern Med 2006; 45: 1107-1111 – reference: 11) Hollerer I, Bachmann A, Muckenthaler MU. Pathophysiological consequences and benefits of HFE mutations: 20 years of research. Haematologica 2017; 102: 809-817 – reference: 19) Fujihara J, Yasuda T, Kimura-Kataoka K, et al. Association of SNPs in transferrin and transferrin receptor genes with blood iron levels in human. Leg Med (Tokyo) 2019; 36: 17-20 – reference: 20) Pichler I, Minelli C, Sanna S, et al. Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. Hum Mol Genet 2011; 20: 1232-1240 – reference: 4) Bomford A. Genetics of haemochromatosis. Lancet 2002; 360: 1673-1681 – reference: 6) Hayashi H, Yano M, Urawa N, et al. A 10-year follow-up study of a Japanese family with ferroportin disease A: mild iron overload with mild hyperferritinemia co-occurring with hyperhepcidinemia may be benign. Intern Med 2018; 57: 2865-2871 – reference: 10) Barton JC, Edwards CQ, Acton RT. HFE gene: Structure, function, mutations, and associated iron abnormalities. Gene 2015; 574: 179-192 – reference: 18) Majore S, Ricerca BM, Radio FC, et al. Type 3 hereditary hemochromatosis in a patient from sub-Saharan Africa: is there a link between African iron overload and TFR2 dysfunction? Blood Cells Mol Dis 2013; 50: 31-32 – reference: 13) Bardou-Jacquet E, Ben Ali Z, Beaumont-Epinette MP, et al. Non-HFE hemochromatosis: pathophysiological and diagnostic aspects. Clin Res Hepatol Gastroenterol 2014; 38: 143-154 – reference: 15) Hattori A, Wakusawa S, Hayashi H, et al. AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with hemochromatosis. Hepatol Res 2003; 26: 154-156 – reference: 1) Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet 2016; 388: 706-716 – reference: 9) Girelli D, Trombini P, Busti F, et al. A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis. Haematologica 2011; 96: 500-506 – reference: 7) Kawabata H, Yang R, Hirama T, et al. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem 1999; 274: 20826-20832 – reference: 8) Radio FC, Majore S, Binni F, et al. TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy. Blood Cells Mol Dis 2014; 52: 83-87 – reference: 2) Ikuta K, Hatayama M, Addo L, et al. Iron overload patients with unknown etiology from national survey in Japan. Int J Hematol 2017; 105: 353-360 – reference: 3) Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 2010; 139: 393-408 – reference: 16) Koyama C, Wakusawa S, Hayashi H, et al. Two novel mutations, L490R and V561X, in the transferrin receptor 2 in Japanese patients with hemochromatosis. Haematologica 2005; 90: 302-307 |
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| Title | TfR2ヘテロ接合型変異で発症したヘモクロマトーシスの1例 |
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