No evidence for the reversal of adrenal failure after hematopoietic cell transplantation in X-linked adrenoleukodystrophy.
No evidence for the reversal of adrenal failure after hematopoietic cell transplantation in X-linked adrenoleukodystrophy.
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没有证据表明 X 连锁肾上腺脑白质营养不良患者造血细胞移植后肾上腺功能衰竭可逆转。
DOI：
10.1038/bmt.2012.33
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发表时间：
2012
影响因子：
4.8
通讯作者：
Orchard,PJ
中科院分区：
文献类型：
--
作者：
Petryk,A;Polgreen,LE;Chahla,S;Miller,W;Orchard,PJ
X-连锁肾上腺脑白质营养不良(ALD)是一种以饱和的超长链脂肪酸(VLCFA)主要聚集在肾上腺皮质、中枢神经系统和睾丸为特征的过氧素体疾病。ALD是由ABCD1基因突变引起的，ABCD1基因编码一种过氧化物体膜运输蛋白。1过氧化体功能障碍和VLCFA积聚之间的联系还不完全清楚。尽管VLCFA的过氧体β氧化受损已被证明具有一定的作用，但也有人提出了独立于过氧体β氧化的机制。2终末器官受累的严重程度和进展速度因患者而异。神经系统疾病是最具破坏性的表现，在儿童时期表现为快速进展的脑性ALD，或在成年时表现为肾上腺脊髓神经病，一种缓慢进展的脊髓疾病，或两者兼而有之。肾上腺皮质功能不全(AI)，无论是亚临床的还是显性的，都存在于大多数ALD患者中，并且可能出现在高达92%的脑部疾病的儿童中。如果在疾病过程的早期进行，造血细胞移植(HCT)是唯一被明确证明可以阻止神经系统疾病进展的治疗方法。4血细胞比容对肾上腺功能的影响知之甚少。这项研究的目的是检验HCT是否可以保留ALD患者的正常肾上腺功能或逆转AI。
X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by accumulation of saturated very long-chain fatty acids (VLCFA) primarily in the adrenal cortex, central nervous system and testes. ALD results from mutations in the ABCD1 gene, which encodes a peroxisomal membrane transport protein. 1 The link between peroxisomal dysfunction and accumulation of VLCFA is not completely understood. Although impaired peroxisomal β-oxidation of VLCFA has been shown to have a role, mechanisms independent of the peroxisomal β-oxidation have also been proposed. 2The severity and tempo of progression of end-organ involvement vary among patients. Neurological disease is the most devastating manifestation, presenting either during childhood as rapidly progressive cerebral ALD or during adulthood as adrenomyeloneuropathy, a slowly progressive disease of the spinal cord, or both. Adrenal insufficiency (AI), either subclinical or overt, is found in the majority of patients with ALD, and may be present in up to 92% of children with cerebral disease. 3 Hematopoietic cell transplantation (HCT) is the only treatment definitively shown to halt neurological disease progression if performed early in the disease process. 4 Much less is known about the effects of HCT on adrenal function. The goal of this study was to examine if HCT can preserve normal adrenal function or reverse AI in ALD patients.