肾上腺脑白质营养不良两种表型的临床及影像学分析

Clinical and Imaging Analysis of Two Different Phenotypes of Adrenoleukodystrophy

目的:探讨肾上腺脑白质营养不良(ALD)的临床特征及诊断方法。方法:回顾性分析3例ALD患者的临床表现、影像特征、治疗和随访结果。结果:病例1为青少年男性,儿童期起病,表现为癫痫、视觉听觉、认知功能及运动功能障碍,伴肾上腺皮质功能低下表现,颅脑MRI显示双侧顶叶、枕叶皮质下白质长T1长T2、T2Flair高信号影,血清极长链饱和脂肪酸水平(VLCFA)增高,诊断为儿童大脑型ALD,给予抗癫痫治疗,糖皮质激素替代治疗,随访3个月,癫痫控制良好,认知功能无改善。病例2和病例3为成年男性,表现为痉挛性截瘫、感觉性共济失调。头颅MRI均显示双侧延髓、桥脑腹侧、大脑脚多发长T1长T2、T2Flair高信号影,提示脑干锥体束受累,病例2脊髓MRI显示全脊髓纤细萎缩,病例3脊髓MRI显示脊髓后索、侧索受累。病例2有排尿障碍、阳痿,舅舅有类似病史,神经传导示双侧胫神经、腓总神经运动电位及感觉电位均未引出,ABCD1基因诊断为c.358dupC(p.R120Pfs*75)新型半合子突变,诊断为肾上腺脊髓神经病型ALD(AMN),随访2年,症状逐渐加重。病例3伴肾上腺皮质功能低下表现,血清VLCFA水平增高,神经传导示双侧胫神经、腓总神经感觉纤维损害,ABCD1基因诊断为c.1553G>A(Arg518Gln),诊断AMN,随访7年余,症状逐渐加重。患者母亲及姐姐ABCD1基因检测均检测到该致病突变。结论:儿童大脑型ALD以肾上腺和脑白质受累为主要表现,AMN以脊髓和周围神经受累为主要表现,脑白质和肾上腺可不受累。血清VLCFA水平增高和基因诊断是确诊ALD的重要依据,目前主要是对症支持治疗。

Objective: To investigate clinical features and diagnosis methods of adrenoleukodystrophy(ALD).Methods: Clinical manifestations, imaging findings, medical treatment, and follow-up study of 3 ALD patients were retrospectively reviewed. Results: Case 1 was an adolescent male with childhood onset of disease. The clinical manifestations were epilepsy, visual impairment, hearing impairment, cognitive impairment, motor dysfunction, and adrenocortical dysfunction. Brain MRI of the patient showed long T1 and T2 and high T2 Flair signal intensities in the bilateral parietal lobe and occipital lobe white matter. The clinical diagnosis of the patient was childhood cerebral form ALD. After antiepileptic therapy and glucocorticoid replacement therapy, seizure did not recur and there was no significant improvement in cognitive dysfunction at 3-months of follow-up. Cases 2 and 3 were adult males. The clinical manifestations were spastic paraplegia and sensory ataxia. Brain MRI of both patients showed multiple long T1 and T2 and high T2 Flair signal intensities in the bilateral medulla oblongata,ventral pons, and cranial feet, indicating damage to the brainstem. MRI of the spinal cord in case 2 showed the entire spinal cord was slender and atrophic. MRI of the spinal cord in case 3 showed damage to the posterior cord and lateral cord. Case 2 presented urination disorder and impotence with family history(the patient’s uncle had a similar disease history). Nerve conduction examination showed that the bilateral tibial nerve, common peroneal nerve, motor potential, and sensory potential were not elicited. ABCD1 genetic diagnosis revealed a new hemizygous mutation c.358 dupC(p.R120 Pfs*75). The patient was diagnosed with adrenomyelo-neuropathy(AMN) and was followed up for 2 years, experiencing a gradual aggravation of symptoms. Case 3 displayed adrenocortical dysfunction and significantly increased serum levels of very long chain fatty acids(VLCFA).Nerve conduction examination showed sensory fiber damage of the bilateral tibial nerve and common peroneal nerve. ABCD1 genetic diagnosis showed the mutation c.1553 G>A(Arg518 Gln). The patient was diagnosed with AMN and was followed up for more than 7 years during which symptoms gradually worsened. The mother and sister of the patient carried the same genetic variation in the ABCD1 gene. Conclusion: Childhood cerebral form ALD is mainly manifested by adrenal and white matter involvement. AMN is mainly manifested by spinal and peripheral nerve involvement, but the adrenal glands and white matter may not be damaged. Increased plasma VLCFA levels and genetic testing are key aspects of ALD diagnosis. Currently the therapeutic method of this disease is primarily symptomatic treatment.