Moser Hugo W, Mahmood Asif, Raymond Gerald V
Neurogenetics Research Center, Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA.
Nat Clin Pract Neurol. 2007 Mar;3(3):140-51. doi: 10.1038/ncpneuro0421.
X-linked adrenoleukodystrophy (X-ALD) is caused by a defect in the gene ABCD1, which maps to Xq28 and codes for a peroxisomal membrane protein that is a member of the ATP-binding cassette transporter superfamily. X-ALD is panethnic and affects approximately 1:20,000 males. Phenotypes include the rapidly progressive childhood, adolescent, and adult cerebral forms; adrenomyeloneuropathy, which presents as slowly progressive paraparesis in adults; and Addison disease without neurologic manifestations. These phenotypes are frequently misdiagnosed, respectively, as attention-deficit hyperactivity disorder (ADHD), multiple sclerosis, or idiopathic Addison disease. Approximately 50% of female carriers develop a spastic paraparesis secondary to myelopathic changes similar to adrenomyeloneuropathy. Assays of very long chain fatty acids in plasma, cultured chorion villus cells and amniocytes, and mutation analysis permit presymptomatic and prenatal diagnosis, as well as carrier identification. The timely use of these assays is essential for genetic counseling and therapy. Early diagnosis and treatment can prevent overt Addison disease, and significantly reduce the frequency of the severe childhood cerebral phenotype. A promising new method for mass newborn screening has been developed, the implementation of which will have a profound effect on the diagnosis and therapy of X-ALD.
X连锁肾上腺脑白质营养不良（X-ALD）由ABCD1基因缺陷引起，该基因定位于Xq28，编码一种过氧化物酶体膜蛋白，它是ATP结合盒转运体超家族的成员。X-ALD具有全种族性，每20000名男性中约有1人受影响。其表型包括快速进展的儿童、青少年和成人脑型；肾上腺脊髓神经病，表现为成人缓慢进展的双下肢轻瘫；以及无神经系统表现的艾迪生病。这些表型常分别被误诊为注意力缺陷多动障碍（ADHD）、多发性硬化症或特发性艾迪生病。约50%的女性携带者会继发与肾上腺脊髓神经病相似的脊髓病变，从而出现痉挛性双下肢轻瘫。检测血浆、培养的绒毛膜绒毛细胞和羊水细胞中的极长链脂肪酸，以及进行突变分析，可实现症状前诊断和产前诊断，以及携带者鉴定。及时使用这些检测方法对于遗传咨询和治疗至关重要。早期诊断和治疗可预防明显的艾迪生病，并显著降低严重儿童脑型的发生率。已开发出一种有前景的新生儿大规模筛查新方法，其实施将对X-ALD的诊断和治疗产生深远影响。
