Fasano Alfonso, Colosimo Cesare, Miyajima Hiroaki, Tonali Pietro Attilio, Re Thomas J, Bentivoglio Anna Rita
Istituto di Neurologia, Università Cattolica del Sacro Cuore, Roma, Italy.
Mov Disord. 2008 Apr 15;23(5):751-5. doi: 10.1002/mds.21938.
Hereditary aceruloplasminemia (HA) is a rare inherited disease characterized by anemia, iron overload, diabetes, and neurodegeneration. HA is caused by the homozygous mutation of the ceruloplasmin (CP) gene. We report two siblings with markedly different phenotypes carrying a novel mutation: a homozygous deletion of two nucleotides (1257-1258 TT del) causing the premature stop of the Cp protein translation (Y401X). An early diagnosis of iron overload was made in the female sibling who was subsequently treated with deferoxamine. At the age of 54, her neurologic symptoms were limited to mild akinetic signs and a history of seizures; moreover, her fasting blood glucose level never exceeded 120 mg/dL. The male sibling, who had not received any specific treatment for HA, developed severe diabetes at the age of 32 and at 48 manifested a progressively disabling neurologic disease. Possible physiopathological bases of these intrafamilial phenotypic variations are discussed.
遗传性血浆铜蓝蛋白缺乏症（HA）是一种罕见的遗传性疾病，其特征为贫血、铁过载、糖尿病和神经退行性变。HA由血浆铜蓝蛋白（CP）基因的纯合突变引起。我们报告了两名携带新突变且具有明显不同表型的同胞：两个核苷酸（1257 - 1258 TT缺失）的纯合缺失导致Cp蛋白翻译提前终止（Y401X）。女性同胞被早期诊断为铁过载，随后接受了去铁胺治疗。54岁时，她的神经症状仅限于轻度运动不能体征和癫痫发作史；此外，她的空腹血糖水平从未超过120 mg/dL。未接受任何针对HA的特异性治疗的男性同胞，在32岁时患了严重糖尿病，并在48岁时表现出进行性致残的神经疾病。本文讨论了这些家族内表型变异可能的生理病理基础。
