迟发型和非迟发型肝豆状核变性的对比研究

摘要

Objective To evaluate the clinical manifestations, metal metabolism, imaging characteristics and treatment response in patients with delayed Wilson disease (WD). Methods Patients with untreated WD (40 with delayed onset and 40 with non?delayed onset) were enrolled. Twenty healthy people were included as normal controls. All patients were evaluated with modified Young scale neural symptom scores, grade of Child liver function and mental symptoms rating scale, magnetic resonance imaging (MRI) scan, magnetic sensitive imaging (susceptibility weighted imaging, SWI), metal metabolism. Corrected phase (CP) was measured at SWI. After 2 week treatment, neurologic symptoms, liver function, and metal metabolism were reviewed. Results The total score of neurological symptoms in WD patients with delayed onset was lower than that of non?delayed onset (13.00 ± 6.87 vs. 21.13 ± 5.53, P=0.033). The scores of SCL?90 and HAMA depression scales in patients with delayed onset were lower than those of non?delayed onset. On T2 weighted imaging, areas including substantia nigra and thalamus, the caudate nucleus, globus pallidus, putamen presented high signal rate in patients with delated onset than those with non?delayed (P=0.022, 0.037, 0.022, 0.037, 0.029 respectively). The SWI CP values of cangbai sphere and shell nucleus in patients with delayed onset were lower than those with non?delayed onset. Patients with delayed onset had higher urinary copper than those with non?delayed onset before and after treatment (P=0.040, 0.036). After treatment, the score of abnormal tremor and gait in patients with delayed onset was decreased (P=0.037, 0.044), while as the occurrence of neurological symptoms was increased by 10%, and the liver function level in patients with delayed WD was decreased in 3 cases. Conclusions The brain of WD patients with delayed onset is mainly composed of metal deposits, however the cell damage is not apparent. Clinical symptoms are characterized by significant liver injury, but relatively mild neurological and psychiatric symptoms. Patients with delayed WD have higher urinary copper excretion than those with non?delayed WD. Chelating agents improves the neurological symptoms in patients with delayed onset.%目的 肝豆状核变性又称Wilson病(WD).拟通过对迟发型与非迟发型WD患者临床症状、金属代谢、影像学、基因类型、对治疗的反应进行对比,探讨有些WD患者症状迟发的原因.方法 选取中山大学附属第一医院未经治疗的WD患者80例(迟发型40例,非迟发型40例),正常对照20例.所有患者进行以下检查或评价:改良Young量表进行神经症状评分、Child肝功能分级、精神症状量表评分、基因测序、磁共振平扫、磁敏感加权成像(SWI)、金属代谢状况.在SWI上测量感兴趣区(ROI)的相位值.二巯丙磺钠治疗2周后,复查神经症状评分、肝功能分级、金属代谢指标.结果迟发型WD患者神经症状总评分低于非迟发型患者[(13.00±6.87)分比(21.13±5.53)分,P=0.033].迟发型患者的精神症状自评量表(SCL?90量表)、Hamilton焦虑、抑郁量表(HAMA)得分低于非迟发型患者.在T2成像上,迟发型患者黑质、丘脑、尾状核、苍白球、壳核的T2高信号比例低于非迟发型患者(P=0.022,0.037,0.490,0.032,0.029).迟发型患者苍白球、壳核的SWI的相位值较非迟发型患者低(P=0.020,0.038).迟发型患者1708?1G>C、1168A>G、3140A>T基因突变比例高于非迟发型患者.迟发型患者治疗前、后的尿铜高于非迟发型患者(P=0.040,0.036).治疗后,迟发型患者震颤、步态异常得分降低(P=0.037,0.044),出现神经症状加重的比例为10%,3例迟发型患者肝功能等级下降.结论 基因突变可能与某些WD患者症状迟发有关.与非迟发型WD患者相比,迟发型患者脑部以金属沉积为主,细胞损伤不明显;临床症状特点是肝脏损伤明显,而神经、精神症状较轻;迟发型患者对排铜治疗反应良好.