肾上腺脊髓神经病的临床和遗传学特点分析

Clinical and genetic characteristics of adrenomyeloneuropathy

目的探讨肾上腺脊髓神经病(AMN)患者的临床及遗传学特点。方法回顾性收集并分析2008年5月至2022年8月在上海交通大学医学院附属第六人民医院就诊并经基因检测确诊的AMN患者的临床资料,对不同基因突变类型患者的临床特征进行比较。使用Loes评分对患者的脑白质脱髓鞘严重程度进行评分,比较有或无脑白质脱髓鞘患者血清极长链脂肪酸(VLCFA)水平的差异。采用扩展残疾状况量表(EDSS)对患者的运动功能进行评分,分析EDSS评分与患者病程之间的相关性。结果共收集23例AMN患者,均为男性,发病年龄(29.52±9.91)岁。所有患者均以下肢异常起病,其中17例首发症状为下肢僵硬、无力(73.9%,17/23),6例为下肢麻木、酸痛(26.1%,6/23)。患者的症状、体征与基因突变类型无关。33.3%(7/21)的患者在(7.67±4.46)年的病程中出现脑白质脱髓鞘。在白质脱髓鞘和无脱髓鞘患者中,患者血清VLCFA水平差异无统计学意义。患者的病程与EDSS评分呈正相关(r=0.57,P=0.006)。在23例AMN患者中共发现16种ABCD1基因突变,其中c.5_19delinsTCTCCAGG(p.P2Lfs^(*)12)突变为新发变异,既往未见报道。有4个来自不同家系的先证者均携带c.1415_1416del(p.Q472Rfs^(*)83)变异。结论AMN以下肢运动及感觉功能障碍为突出表现,运动功能的恶化与病程呈正相关。AMN有向脑型转化的风险,血清VLCFA的浓度与表型转换无关。ABCD1基因的c.1415_1416del(p.Q472Rfs^(*)83)突变为该疾病的热点突变。

Objective To summarize and analyze the clinical and genetic characteristics of Chinese patients with adrenomyeloneuropathy(AMN).Methods Clinical data were collected and analyzed retrospectively on AMN patients who were diagnosed by genetic testing in Shanghai Sixth People′s Hospital,Shanghai Jiao Tong University School of Medicine from May 2008 to August 2022.Clinical characteristics of AMN patients with different types of gene mutations were compared.Loe score was used to evaluate the severity of white matter demyelinating,and the serum levels of very long-chain fatty acids(VLCFA)in patients with or without white matter demyelinating were compared.The motor function of the AMN patients was assessed using the Expanded Disability Status Scale(EDSS),and the association between EDSS scores and the course of disease was analyzed.Results A total of 23 male patients with onset age of(29.52±9.91)years were included in this study.The first symptom of all patients was abnormal lower extremities,of which 17 patients showed stiffness and weakness in their lower limbs(73.9%,17/23),and 6 patients showed numbness and pain in both lower limbs(26.1%,6/23).The occurrence of symptoms was not related to the type of gene mutation.White matter demyelination occurred in 33.3%(7/21)of patients over a disease duration of(7.67±4.46)years.There was no statistically significant difference in serum VLCFA level between the white-matter demyelination group and the non-demyelination group.The EDSS score was positively correlated with the disease duration(r=0.57,P=0.006).Sixteen ABCD1 gene mutations were found in this study,among which c.5_19delinsTCTCCAGG(p.P2Lfs^(*)12)was reported for the first time.Four probands belonging to different families carried the c.1415_1416del(p.Q472Rfs^(*)83)variant.Conclusions Lower limb movement disorders and sensory dysfunction are the prominent clinical manifestations in AMN patients,with deterioration of motor function associated with the course of disease.AMN may be converted to cerebral type and VLCFA concentration is not associated with the phenotypic changes.The c.1415_1416del(p.Q472Rfs^(*)83)mutation is a hot spot mutation of the disease.