Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: a case report.
Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: a case report.
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DOI：
10.1186/s12876-021-01674-z
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发表时间：
2021-03-05
影响因子：
2.4
通讯作者：
Hino K
中科院分区：
文献类型：
--
作者：
Nishina S;Tomiyama Y;Ikuta K;Tatsumi Y;Toki Y;Kato A;Kato K;Yoshioka N;Sasaki K;Hara Y;Hino K
遗传性血色病是一组异质性遗传性铁超负荷条件，其特征是增加肠道吸收和沉积在重要器官。铁调素是一种可溶性调节剂，通过铁转运蛋白-1（铁输出蛋白）的内化作用减弱肠铁吸收和网状内皮巨噬细胞的铁释放。膜铁转运蛋白病是一种遗传性血色素沉着症，受膜铁转运蛋白-1基因SLC 40 A1影响，表型分为两种形式（经典型和非经典型）。在非经典形式中，膜铁转运蛋白突变负责获得具有完全铁输出能力的功能，但对铁调素的下调不敏感。在这里，我们报告一例非经典的ferroportin病。一名46岁的日本男性显示血清铁（284 μg/dl）、铁蛋白（1722 ng/ml）、转铁蛋白饱和度（91.3%）和铁调素-25水平（139.6 ng/ml）升高。磁共振成像（MRI）显示T1和T2加权图像中肝脏信号强度明显降低。肝组织学显示大量铁主要蓄积在肝细胞中。我们在SLC 40 A1基因中发现了一个杂合的1520 A> G（p.H507R）突变。该患者每月进行静脉切开术（每次400 ml），持续3年。重要的是，血清铁蛋白水平正常时，血清铁调素水平（1.0 ng/ml）是正常的，肝脏铁积累显着减少后3年的放血。本病例首次证明，在SLC 40 A1中具有p.H507R突变的膜铁转运蛋白疾病患者中，通过MRI测量的肝铁水平与通过长期静脉切开术测量的血清铁调素水平之间存在相关性。
Hereditary hemochromatosis is a heterogenous group of inherited iron-overload conditions that is characterized by increased intestinal absorption and deposition in vital organs. Hepcidin is a soluble regulator that acts to attenuate both intestinal iron absorption and iron release from reticuloendothelial macrophages through internalization of ferroportin-1, an iron exporter. Ferroportin disease is hereditary hemochromatosis which is affected by SLC40A1, a gene coding ferroportin-1, and phenotypically classified into two forms (classical and nonclassical). In nonclassical form, ferroportin mutations are responsible for a gain of function with full iron export capability but insensitivity to downregulation by hepcidin. Here, we report a case of nonclassical ferroportin disease. A 46-year-old Japanese man showed elevated serum iron (284 μg/dl), ferritin (1722 ng/ml), transferrin saturation ratio (91.3%), and hepcidin-25 level (139.6 ng/ml). Magnetic resonance imaging (MRI) demonstrated a marked reduction in the signal intensity of the liver in T1- and T2-weighted images. The liver histology exhibited a large amount of iron that had accumulated predominantly in hepatocytes. We identified a heterozygous 1520A > G (p.H507R) mutation in the SLC40A1 gene. Phlebotomy (400 ml at a time) was monthly performed for 3 years in this patient. Importantly, the serum hepcidin level (1.0 ng/ml) was normal when the serum ferritin level was normal and hepatic iron accumulation was remarkably reduced after 3 years of phlebotomy. The present case demonstrated for the first time that there was a correlation between hepatic iron levels as measured by MRI and serum hepcidin levels through long-term phlebotomy in a patient with ferroportin disease with the p.H507R mutation of in SLC40A1.
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DOI：
10.1007/978-981-13-7979-6_4
发表时间：
2019-01-01
期刊：
EVOLVING LANDSCAPE OF LIVER CIRRHOSIS MANAGEMENT
影响因子：
--
作者：
Hino, Keisuke;Nishina, Sohji
通讯作者：
Nishina, Sohji
影响因子：
2.2
作者：
Hattori, Ai;Miyajima, Hiroaki;Wakusawa, Shinya
通讯作者：
Wakusawa, Shinya
影响因子：
25.7
作者：
Mayr R;Janecke AR;Schranz M;Griffiths WJ;Vogel W;Pietrangelo A;Zoller H
通讯作者：
Zoller H
影响因子：
4.8
作者：
Park, CH;Valore, EV;Ganz, T
通讯作者：
Ganz, T
影响因子：
2.3
作者：
Sham, RL;Phatak, PD;Beutler, E
通讯作者：
Beutler, E