Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Lancet Child Adolesc Health. 2021 Jul;5(7):524-530. doi: 10.1016/S2352-4642(20)30392-8. Epub 2021 Apr 15.
Juvenile haemochromatosis is a severe inherited iron-loading disorder that can present in children and adolescents. Typical manifestations include heart failure, endocrine failure (including diabetes and hypogonadism), cirrhosis, and arthropathy. Compared with HFE haemochromatosis, juvenile haemochromatosis affects female and male individuals similarly, presents at a younger age, and causes multiple organ dysfunction; the principle of iron loading into tissues from the gut is shared by both forms, but the process is far more rapid in juvenile haemochromatosis. Juvenile haemochromatosis is initially recognised by extreme increases of serum ferritin and transferrin saturation, which is supported by an MRI showing iron deposition in the heart and liver. MRI software techniques allow quantification of iron in these organs, and can therefore be used to monitor progress. Juvenile haemochromatosis is autosomal recessive and is generally associated with mutations in HJV (type 2A) or HAMP (type 2B). Mutations in TFR2 cause an intermediate severity phenotype (type 3), but this phenotype can cross over into the juvenile haemochromatosis spectrum so it might need to be additionally considered during diagnosis. Treatment needs to be administered without delay, in the form of aggressive iron chelation, and a multidisciplinary approach is essential. Because iron is removed, organ function is restored, which could obviate the need for cardiac or liver transplantation. Substantial restoration of health can ensue, but patients require life-long monitoring. Family screening is an important component of the management of juvenile haemochromatosis. Genetic advances which underpin the haemochromatosis types also clarify the role of iron metabolism in health and disease, particularly the role of hepcidin in regulating iron homoeostasis. Therefore, juvenile haemochromatosis is an important condition to understand; it can present insidiously in children and adolescents, and awareness of the diagnosis is needed to inform early recognition and treatment.
青少年血色病是一种严重的遗传性铁过载疾病，可发生于儿童和青少年。典型表现包括心力衰竭、内分泌功能衰竭（包括糖尿病和性腺功能减退）、肝硬化和关节炎。与 HFE 血色病相比，青少年血色病影响男女患者的方式相似，发病年龄更早，并导致多器官功能障碍；两种形式的铁从肠道进入组织的加载原理是相同的，但在青少年血色病中铁的加载过程要快得多。通过血清铁蛋白和转铁蛋白饱和度的极度升高，最初可识别出青少年血色病，这一结果得到 MRI 显示心脏和肝脏铁沉积的支持。MRI 软件技术可定量评估这些器官中的铁含量，因此可用于监测进展情况。青少年血色病为常染色体隐性遗传，通常与 HJV（2A 型）或 HAMP（2B 型）突变相关。TFR2 突变引起中等严重程度的表型（3 型），但这种表型可跨越到青少年血色病谱，因此在诊断过程中可能需要额外考虑。需要立即开始积极的铁螯合治疗，采取多学科方法进行治疗。由于铁被去除，器官功能得以恢复，这可能避免了心脏或肝脏移植的需要。大量恢复健康是可能的，但患者需要终身监测。家族筛查是青少年血色病管理的重要组成部分。为血色病类型提供基础的遗传进展也阐明了铁代谢在健康和疾病中的作用，特别是铁调素在调节铁稳态中的作用。因此，青少年血色病是一种需要了解的重要疾病；它可能在儿童和青少年中隐匿性出现，需要对这种疾病有认识，以便早期识别和治疗。
