Lenzhofer Markus, Schroedl Falk, Trost Andrea, Kaser-Eichberger Alexandra, Wiedemann Helmut, Strohmaier Clemens, Hohensinn Melchior, Strasser Michael, Muckenthaler Martina U, Grabner Guenther, Aigner Elmar, Reitsamer Herbert A
*MD †Dr rer nat ‡PhD Department of Ophthalmology and Optometry (ML, FS, AT, AK-E, CS, MH, GG, HAR), Department of Anatomy (FS), Department of Laboratory Medicine (HW), and First Department of Internal Medicine (MS, EA), Paracelsus Medical University, Salzburg, Austria; Department of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, Germany (MUM); and Molecular Medicine Partnership Unit, Heidelberg, Germany (MUM).
Optom Vis Sci. 2015 Apr;92(4 Suppl 1):S40-7. doi: 10.1097/OPX.0000000000000544.
Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens.
During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed.
Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene.
In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.
遗传性高铁蛋白血症白内障综合征（HHCS）是一种罕见的常染色体显性遗传病，其特征为高铁蛋白血症，但体内无铁过量且双侧白内障发病较早。尽管已有报道HHCS患者血清铁蛋白浓度升高5至20倍，但尚未获得房水中铁蛋白水平的数据。因此，我们旨在研究房水和血清中的铁蛋白水平，并进一步提供晶状体的组织学和超微结构数据。
在一位37岁HHCS患者进行白内障摘除和人工晶状体植入手术期间，从其双眼获取房水和晶状体吸出物。通过免疫测定法对HHCS患者和健康对照者（n = 6）的血清和房水中的铁蛋白水平进行定量分析。对HHCS患者的晶状体吸出物进行组织学和超微结构分析。此外，通过聚合酶链反应和血液DNA测序进行基因突变筛查。
对照组血清铁蛋白水平为142.2±38.7μg/L，而HHCS患者的这一参数则过度升高（1086μg/L）。房水中铁蛋白分析显示，正常对照者为6.4±3.8μg/L，HHCS患者右眼为146.3μg/L，左眼为160.4μg/L。DNA分析在轻链铁蛋白（L-铁蛋白）基因的铁反应元件中检测到第18位的C>A突变、第22位的T>G突变、第24位的T>C突变以及第26位的T>G多态性。
在HHCS患者中，检测到房水中铁蛋白水平升高了23倍（右眼）至25倍（左眼）。因此，HHCS中双侧白内障的形成很可能是房水铁蛋白升高的结果。此外，还报道了这种罕见疾病在L-铁蛋白基因铁反应元件中的一种新突变。
