家族性ⅣA型遗传性血色病1例报告

范艳玲; 李艳萌; 武祯; 武丽娜; 欧晓娟; 黄坚; 张伟

doi:10.12449/JCH260922

家族性ⅣA型遗传性血色病1例报告

DOI: 10.12449/JCH260922

范艳玲^{1, 2, 3},
李艳萌^{2, 3, 4},
武祯^{1, 2, 3},
武丽娜^{1, 2, 3},
欧晓娟^{1, 2, 3},
黄坚^{2, 3, 4},
张伟^{1, 2, 3, , ,}

1.
首都医科大学附属北京友谊医院肝病中心，北京 100050
2.
消化健康全国重点实验室，北京 100050
3.
消化系统疾病国家临床医学研究中心，北京 100050
4.
首都医科大学附属北京友谊医院北京市临床医学研究所分子生物学实验室，北京 100050

基金项目:

国家自然科学基金 (82070598);

北京市医院管理中心消化内科学科协同发展中心项目 (XXZ0501);

北京市医院管理中心消化内科学科协同发展中心项目 (XXZ0502)

伦理学声明：本例报告已获得患者及家属知情同意。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：范艳玲负责文章初稿的撰写与数据整理；李艳萌、黄坚负责基因检测分析与方法学验证；武丽娜、武祯和欧晓娟负责病例的临床诊断、家系追踪与资料收集；张伟负责全文的核验、修改与最终审定。

详细信息

通信作者:
张伟， zhangwei2020@ccmu.edu.cn （ORCID： 0000-0002-9814-2431）

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出版历程
- 收稿日期: 2025-12-21
- 录用日期: 2026-02-04
- 出版日期: 2026-09-25

Familial type ⅣA hereditary hemochromatosis: A case report

Yanling Fan^{1, 2, 3},
Yanmeng Li^{2, 3, 4},
Zhen Wu^{1, 2, 3},
Lina Wu^{1, 2, 3},
Xiaojuan Ou^{1, 2, 3},
Jian Huang^{2, 3, 4},
Wei Zhang^{1, 2, 3
, ,
,}

1.
Liver Research Center，Beijing Friendship Hospital，Capital Medical University，Beijing 100050，China
2.
State Key Laboratory of Digestive Health，Beijing 100050，China
3.
National Clinical Research Center for Digestive Diseases，Beijing 100050，China
4.
Molecular Biology Laboratory，Beijing Clinical Research Institute，Beijing Friendship Hospital，Capital Medical University，Beijing 100050，China

Research funding:

National Natural Science Foundation of China (82070598);

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0501);

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0502)

More Information

Corresponding author: Zhang Wei， zhangwei2020@ccmu.edu.cn （ORCID： 0000-0002-9814-2431）

摘要

摘要: 遗传性血色病（HH）是一类因铁代谢相关基因突变导致铁过载的遗传性疾病。ⅣA型HH（即经典型膜铁转运蛋白病）由SLC40A1基因功能缺失性变异引起，其临床表现为血清铁蛋白（SF）水平显著升高、转铁蛋白饱和度正常或降低以及脾脏铁沉积明显。本文报道1例ⅣA型HH患者，临床表现为无症状的SF水平显著增高，磁共振成像提示脾脏铁过载明显重于肝脏铁过载，经皮肝脏活组织检查提示轻度脂肪肝、Kupffer细胞铁沉积，基因变异分析检出SLC40A1 c.485_487del（p.Val162del）杂合变异。对家系成员进行筛查，其母亲亦携带相同变异，且伴有肝、脾铁过载表现，进一步证实该变异的致病性。本案例提示，ⅣA型HH起病隐匿，易被误诊；对于无法解释的SF水平持续升高者，即使合并其他肝病，也应积极进行HH基因检测，以实现早期诊断与干预。
- 遗传性疾病，先天性 /
- 膜铁转运蛋白病 /
- 铁过载
Abstract: Hereditary hemochromatosis （HH） is a hereditary disease characterized by iron overload resulting from mutations in genes involved in iron metabolism. Type ⅣA HH， also known as classical ferroportin disease， is caused by loss-of-function mutations in the SLC40A1 gene and has the clinical manifestations of a significant increase in serum ferritin， normal or low transferrin saturation， and marked iron deposition in the spleen. This article reports a case of type ⅣA HH with a significant asymptomatic increase in serum ferritin. Magnetic resonance imaging showed that the severity of iron overload in the spleen was significantly higher than that in the liver； liver biopsy showed mild fatty liver disease and iron deposition in Kupffer cells； gene variation analysis identified a heterozygous mutation in SLC40A1 c.485_487del （p.Val162del）. Screening of family members showed that the proband’s mother carried the same variation and had the manifestation of iron overload in the liver and spleen， which further confirmed the pathogenicity of this variation. This case highlights that type ⅣA HH often has an insidious onset and is frequently misdiagnosed. For patients with an unexplained persistent increase in serum ferritin， active genetic testing for HH should be considered， even in the presence of concurrent liver diseases， in order to realize early diagnosis and intervention.
- Genetic Diseases， Inborn /
- Ferroportin Disease /
- Iron Overload

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注： a～c，腹部核磁：a，肝、脾实质信号弥漫性减低，明显低于椎旁肌；T₁加权像双回波显示肝、脾同相位（b）信号低于反相位（c），提示肝脾铁过载。d，心脏核磁：乳头肌水平前壁T2*值约为16.5 ms，心尖部游离壁心肌T2*值为12.5～16.4 ms。e，小叶结构保留，汇管区见少量淋巴细胞浸润；肝细胞大泡性脂肪变性，范围约5%（苏木精-伊红染色，×400）；f，肝细胞内可见色素沉积，少量Kupffer细胞内可见含铁血黄素沉积（黑色箭头所示）（普鲁士蓝染色，×400）。

图 1 腹部、心脏核磁及肝穿刺病理结果

Figure 1. Abdominal， cardial MRI and histopathological findings of liver biopsy specimens

下载: 全尺寸图片幻灯片

注： a，SLC40A1基因变异c.485_487del，p.Val162del测序图；b，家系分析图。

图 2 SLC40A1基因变异及家系图

Figure 2. Genetic analysis and family pedigree

下载: 全尺寸图片幻灯片

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