Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Department of Gastroenterology, Kitakyushu General Hospital, Kitakyushu, Japan.
Med Mol Morphol. 2021 Mar;54(1):60-67. doi: 10.1007/s00795-020-00259-1. Epub 2020 Jun 30.
Hemochromatosis is a clinical syndrome characterized by iron overload in various organs. We present here a case of type 4 hereditary hemochromatosis due to heterozygous mutation in SLC40A1 gene (p.D157A). SLC40A1 encodes ferroportin, a macromolecule only known as iron exporter from mammalian cells. He first presented symptoms correlated with hypopituitarism. Furthermore, marked hyperferritinemia and high transferrin saturation were revealed in combination with the findings of iron overload in the liver, spleen and pituitary gland by computed tomography and magnetic resonance imaging. Liver biopsy revealed iron deposition in both hepatocytes and Kupffer cells. SLC40A1 mutations are considered to cause wide heterogeneity by various ferroportin mutations. Thus, clinicopathological examinations seem to be very important for diagnosing phenotype of type 4 hemochromatosis in addition to the gene analysis. We diagnosed him as type 4B hereditary hemochromatosis (ferroportin-associated hemochromatosis) by the findings of high transferrin saturation and iron deposition in hepatocytes, and then started iron chelating treatment. We should suspect the possibility of hereditary hemochromatosis even in Japanese with severe iron overload. Although the same mutation in SLC40A1 gene (p.D157A) had been reported to cause "loss of function" phenotype, we considered that the mutation of our case caused "gain of function" phenotype.
血色病是一种以多种器官铁过载为特征的临床综合征。我们在此报告一例 4 型遗传性血色病，其病因是 SLC40A1 基因突变（p.D157A），杂合子突变。SLC40A1 基因编码铁输出蛋白，这是一种仅在哺乳动物细胞中被发现的铁输出大分子。他首次出现与垂体功能减退相关的症状。此外，通过计算机断层扫描和磁共振成像发现肝脏、脾脏和垂体存在铁过载，同时还伴有明显的高血铁蛋白血症和高转铁蛋白饱和度。肝脏活检显示肝细胞和枯否细胞均有铁沉积。SLC40A1 基因突变被认为会导致各种铁输出蛋白突变的广泛异质性。因此，除了基因分析外，临床病理检查对于诊断 4 型血色病表型似乎非常重要。我们根据高转铁蛋白饱和度和肝细胞铁沉积的发现，诊断他为 4B 型遗传性血色病（铁输出蛋白相关血色病），随后开始进行铁螯合治疗。我们应该怀疑遗传性血色病的可能性，即使是在日本人群中，严重的铁过载也可能存在。虽然 SLC40A1 基因突变（p.D157A）曾被报道会导致“功能丧失”表型，但我们认为该病例的突变导致了“功能获得”表型。
