肾上腺脊髓神经病一例诊断和治疗

Precise diagnosis and treatment of adrenomyeloneuropathy:a case report

目的报道1例以双下肢无力、走路不稳为主要表现的肾上腺脊髓神经病(adrenomyeloneuropathy,AMN)患者的诊断和洛伦佐油治疗半年的随访经历,并结合文献讨论AMN诊断及治疗。方法纳入应急总医院2022年9月明确诊断的1例AMN患者,分析患者外周静脉血促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、血皮质醇、血清极长链脂肪酸(very long chain fatty acids,VLCFAs)水平、头颅MRI及AMN相关基因,并观察患者服用洛伦佐油(Lorenzo's Oil)20 mL/d治疗半年后病情变化情况。结果患者治疗前实验室检查结果提示肾上腺皮质功能减退(ACTH水平明显升高,血皮质醇水平明显减低),二十四烷酸(C24:0)、二十六烷酸(C26:0)水平以及C24:0/C22:0、C26:0/C22:0比值等VLCFAs指标增高,脑MRI提示双侧内囊锥体束高信号、大脑脚锥体束稍高信号,高通量全外显子基因测序显示ATP结合超家族D亚组膜1(ATP binding cassette subfamily D member 1,ABCD1)基因(NM-000033)外显子7发生c.1768C>T半合子变异,导致第590位氨基酸由丝氨酸变异为亮氨酸,为错义突变。使用洛伦佐油20 mL/d治疗半年后,临床症状部分好转,复查ACTH、血皮质醇水平等激素指标有所下降,C26:0水平及C24:0/C22:0及C26:0/C22:0比值等VLCFAs指标也均有明显下降。结论以双下肢无力,走路不稳为主要表现的患者,应考虑AMN可能,完善血清极长链脂肪酸和ABCD1基因检测以明确诊断,早诊早治。

Objective To report the diagnosis and treatment of a patient with adrenomyeloneuropathy(AMN)characterized by weakness of both lower limbs and walking impairment.The diagnosis and treatment of Lorenzo's Oil were discussed in combination with the literature.Methods A case of AMN diagnosed precisely in September 2022 in Emergency General Hospital was included.Peripheral venous blood was collected for clinical biochemical indexes such as adrenocorticotropic hormone(ACTH),blood cortisol,and very long chain fatty acids(VLCFAs).Brain MRI and AMN related gene were analysed.After six months of treatment with Lorenzo's oil,the changes of the patient were observed.Results The laboratory examination results of the patients before treatment indicated adrenal cortical dysfunction(ACTH concentration increased significantly,blood cortisol decreased significantly),tetracosanoic acid(C24:0),hexacosanoic acid(C26:0),C24:0/C22:0,C26:0/C22:0 and other VLCFAs increased.Brain MRI showed high signal in pyramidal tract of bilateral internal capsule and slightly high signal in pyramidal tract of cerebral peduncles.High throughput whole exon sequencing showed that the patient had a c.1768C>T hemizygous mutation in exon 7 of ABCD1 gene(NM-000033),the result amino acid at position 590 was changed from serine to leucine,which was a missense mutation.After six months of treatment with Lorenzo's oil,the clinical manifestation of the patient improved partially.ACTH,luteinizing hormone and other hormone indexes were decreased.VLCFAs indexes such as C26:0,C24:0/C22:0 and C26:0/C22:0 also decreased significantly.Conclusions If the patient presents with weakness of both lower limbs and walking instability,AMN should be considered.Plasma very long chain fatty acids and ABCD1 gene variation should be tested as soon as possible to confirm a clear diagnosis for early treatment.