晚发型高苯丙氨酸血症脑白质病变的临床和影像学特征分析  

Clinical and imaging features of late-onset hyperphenylalaninemia leukoencephalopathy

作　　者：仇宇悦 李洁 黄欣莹 王添艺 褚姗姗 金蔚 毛晨晖 高晶 Qiu Yuyue;Li Jie;Huang Xinying;Wang Tianyi;Chu Shanshan;Jin Wei;Mao Chenhui;Gao Jing(Department of Neurology,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院、北京协和医院神经科、疑难重症及罕见病国家重点实验室,100730 [2]中国医学科学院,放射科100730 [3]北京大学深圳医院神经科

出　　处：《北京医学》2024年第7期533-538,共6页Beijing Medical Journal

基　　金：国家重点研发计划(2020YFA0804500、2022YFA0804501);中国医学科学院医学与健康科技创新工程(2021-I2M-1-020);北京协和医院中央高水平医院临床科研专项(2022-PUMCH-A-254、2022-PUMCH-D-007)。

摘　　要：目的探讨未经治疗的青少年起病的晚发型高苯丙氨酸血症(hyperphenylalaninemia,HPA)白质病变的临床和影像学特征。方法选取2015年1月2022年1日北京协和医院神经科经生化和(或)基因确诊的青少年起病HPA患者5例,分析其临床和影像学特征。结果5例患者中男3例、女2例,起病年龄7~15岁,诊断年龄14~20岁。临床表现包括精神发育迟滞、精神行为症状,痉挛步态和癫痫发作。脑白质病变以侧脑室后角旁顶枕叶为中心,逐渐向额叶、半卵圆中心和皮层下白质扩展,早期避开视放射和U形纤维。病变呈持续的DWI高信号,不强化。MRI示白质病变与临床严重程度不匹配,白质病变和皮层萎缩不匹配提示灰质受累。经低苯丙氨酸饮食治疗后,患者神经精神症状保持稳定,但影像学病灶仍可进展。结论青少年起病的HPA常表现为精神发育迟滞或痉挛性瘫痪,伴或不伴其他神经系统症状;影像学白质病变的分布以侧脑室后角旁顶枕叶白质为中心,可随疾病严重程度向更大范围扩展。饮食控制后可稳定临床症状,但影像病灶可继续进展,早期诊断和治疗可改善患者预后和生活质量。Objective To explore the clinical and imaging features of late-onset hyperphenylalaninemia(HPA)leukoencephalopathy in untreated adolescents.Methods A total of five patients with adolescent-onset HPA,diagnosed by biochemistry and(or)gene in the Department of Neurology,Peking Union Medical College Hospital from January 2015 to January 2022 were selected,and the clinical and imaging features were analyzed.Results Among the five patients,there were three males and two females with the onset age of 7 to 15 years,and the diagnosis age was 14 to 20 years old.Clinical manifestations included mental retardation,psychobehavioral symptoms,spastic gait and seizures.The white matter lesions were centered in the parieto-occipital lobe adjacent to the posterior horn of the lateral ventricle,gradually spreading to the frontal lobe,the semi-oval center and the subcortical white matter,avoiding optic radiation and U-shaped fibers in the early stage.The lesions showed persistent DWI high signal without enhancement.In addition,there were mismatches between the white matter lesions seen on MRI and the actual clinical manifestations,and the mismatch between white matter lesions and cortical atrophy suggested gray matter involvement.After low phenylalanine diet treatment,the patient's neuropsychiatric symptoms remained stable,but the imaging lesions could still progress.Conclusions The onset HPA of adolescents is often characterized by mental retardation or spastic paralysis,with or without other nervous system symptoms.The distribution of imaging white matter lesions is centered on the white matter of parietal occipital lobe near the posterior horn of lateral ventricle,which can expand to a wider range with the severity of the disease.After diet control,the clinical symptoms can be stabilized,but the imaging lesions can continue to progress.Early diagnosis and treatment can improve the prognosis and quality of life of patients.

关 键 词：高苯丙氨酸血症 苯丙酮尿症 白质 青少年 

分 类 号：R743[医药卫生—神经病学与精神病学] R589.7[医药卫生—临床医学]