五例 X-连锁肾上腺脑白质营养不良的临床分析

摘要

目的 分析X-连锁肾上腺脑白质营养不良(X-ALD )的临床表现、实验室检查和神经影像学特点.方法 回顾性分析5例临床确诊的X-ALD患者临床表现、血浆极长链脂肪酸(VLCFA )水平、肾上腺功能、ABCD1基因突变、影像特征、治疗和随访的结果.结果 5例X-ALD患者均为男童,发病年龄分别为3岁、5岁、6岁、13岁、14岁,其中儿童脑型(childhood cerebral ALD ,CCALD ;＜10岁)3例,青春期脑型(adolescent cer-ebral ALD ,AdolCALD ;10～21岁)2例,病程分别为3.0 、2.0 、1.0 、1.0 、0.5年. 5例均有不同程度的智力障碍和肢体活动障碍,其中1例伴听力下降,1例伴视力下降,1例伴抽搐发作,1例伴发育迟缓、皮肤色素沉着. 3例检测VLCFA水平,血浆二十六酸(C26 :0 )水平(分别为1.1 、1.4 、1.5 μg／mL ) 、二十四酸(C24 :0 )与二十二酸(C22 :0)的比值(C24 :0／C22 :0 ;分别为1.52 、1.55 、2.10) 、C26 :0与C22 :0的比值(C26 :0／C22 :0 ;分别为0.1 、0.07 、0.09)均增高. 3例肾上腺功能减退,表现为血皮质醇(8Am )降低(分别为122 、52 、130 nmol／L) 、ACT H (8Am )升高(分别为 112 、121 、72 ng／L ) . 3 例显示基因突变,分别为 c.1780 + 2T ＞ G 、c. 871G＞ A (p. Glu291Lys) 、c.1849C＞ T (p. Arg617Cys) ,均支持X-ALD诊断. 5例患者头颅M RI均显示顶枕叶白质区对称性蝶翼状长T1及长T2信号,2例增强扫描示病灶周边环状强化. 3例给予氢化可的松激素替代治疗,1例给予抗癫痫治疗,5例均行肢体功能康复训练,疗效不佳.本组患者出院后均随访1～6年,1例患儿死亡,其余4例病情仍在加重.结论 本组X-ALD患者均为男性儿童和青春期脑型.临床特征为进行性听力和视力下降、肢体活动障碍和癫痫发作,均有智力减退.血浆VLCFA水平升高和M RI特征改变是诊断的重要依据,基因检测可确诊.%ABSTRACT : Objective To analyze the clinical characteristics , laboratory examination results and neuroimaging manifestations of X-linked adrenoleukodystrophy ( X-ALD ) . MethodsT he clinical manifestations ,level of plasma very long chain fatty acid (VLCFA ) , adrenal function tests ABCD1 gene mutation analysis ,imaging features ,treatment and follow-up of 5 patients with X-ALD admitted to our hospital were retrospectively analyzed. Results All the patients were boys. T he ages of onset were 3 , 5 , 6 , 13 , 14 years old. T here were 3 Childhood cases , and 2 adolescent 2 cases. T he disease durations were 3 ,2 ,1 ,1 and 0.5 year . 5 patiens had different degrees of intelligent impairment and limb movement disorder associated with auditory disorder , visual disorder , seizures , developmental retardation and skin pigmentation. T he level of VLCFA in 3 patients were increased , C26 : 0 1.1 ,1.4 , 1.5 μg／mL ;C24 : 0／C22 : 0 1.52 ,1.55 ,2.10 ;C26 :0／C22 : 0 0.1 ,0.07 ,0.09. Adrenal insufficiency were found in 3 patints ,characterized by blood cortisol (8Am ) decrease and ACT H (8Am ) increase. 3 cases showed genetic mutations ,namely c.1780 2T ＞ G ,c.871G＞ A (p. Glu291Lys) ,c.1849C＞ T (p. Arg617Cys ) ,supporting the diagnosis of X-ALD. cranial M RI of 5 patients showed the characteristic pattern of symmetrical long Tl and long T 2 signal in the parieto-occipital region ,even involving the splenium of the corpus callosum ,with symmetric linear enhancement in postcontrast T 1-weighted imaginge in 2 patients. 3 patients were given cortisol replacement therapy. 1 patient was given antiepileptic therapy. 5 patients underwent limb function rehabilitation training. 1 patient died and 4 patients’ symptoms aggravated during the 1-6 years followed-up. Conclusions T his group of X-ALD patients were CCALD and AdolCALD. Clinical features included progressive auditory and vision impairment ,physical activity disorders , and seizures ;all the patients had mental retardation. T he elevated level of plasma VLCFA and the characteristic changes of M RI were important basis for diagnosis ,and gene detection could help to confirm the diagnosis.