Nonnenmacher L, Langer T, Blessing H, Gabriel H, Buchwald H-J, Meneksedag C, Kohne E, Gencik M, Debatin K-M, Cario H
Hämatologie und Onkologie, Universitätsklinik für Kinder- und Jugendmedizin, Ulm, Germany.
Klin Padiatr. 2011 Nov;223(6):346-51. doi: 10.1055/s-0031-1287825. Epub 2011 Oct 21.
The hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disorder characterized by high serum ferritin and early onset cataract. Mutations in the iron responsive element (IRE) within the 5' untranslated region of the L-ferritin (FTL) gene lead to constitutive L-ferritin synthesis resulting in hyperferritinemia. Bilateral cataract formation is caused by the intracellular accumulation of ferritin in the lens.
4 children from unrelated families were referred for further exploration of hyperferritinemia which was detected during the diagnostic work-up of gastroenterological or hematological disorders. 1 patient was primarily referred for the investigation of bilateral cataract.Diagnostics included routine blood analysis, including complete blood count, iron status, liver and kidney parameters, a physical and an ophthalmological examination. Molecular genetic analysis of the FTL IRE was performed in 4 patients by PCR from genomic DNA and subsequent direct sequencing.
All index patients presented with isolated hyperferritinemia without iron overload and had a positive family history for early onset cataract. Age at onset and disease severity varied between different families and among family members. Molecular genetic analysis revealed point mutations within the FTL IRE.
In patients with hyperferritinemia but without any other sign of iron overload or inflammation HHCS should be considered to avoid complex and invasive procedures. Vice versa, in patients with familial inherited cataract the early serum ferritin measurement helps to avoid unnecessary diagnostics.
遗传性高铁蛋白血症白内障综合征（HHCS）是一种常染色体显性疾病，其特征为血清铁蛋白水平升高和白内障早发。L-铁蛋白（FTL）基因5'非翻译区内铁反应元件（IRE）的突变导致L-铁蛋白的组成型合成，从而引起高铁蛋白血症。晶状体中铁蛋白的细胞内蓄积导致双侧白内障形成。
4名来自非亲缘家庭的儿童因在胃肠道或血液系统疾病诊断检查期间检测到高铁蛋白血症而前来进一步检查。1名患者最初因双侧白内障检查前来就诊。诊断包括常规血液分析，包括全血细胞计数、铁状态、肝肾功能参数、体格检查和眼科检查。对4名患者的FTL IRE进行了分子遗传学分析，方法是从基因组DNA进行PCR扩增，随后进行直接测序。
所有索引患者均表现为单纯性高铁蛋白血症，无铁过载，且有白内障早发的家族史。发病年龄和疾病严重程度在不同家庭和家庭成员之间有所不同。分子遗传学分析显示FTL IRE内存在点突变。
对于高铁蛋白血症但无任何其他铁过载或炎症迹象的患者，应考虑HHCS，以避免复杂和侵入性操作。反之，对于家族遗传性白内障患者，早期测量血清铁蛋白有助于避免不必要的诊断。
