Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study
Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study
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造血干细胞移植对酰基辅酶A氧化酶缺乏症的影响：同胞比较研究
DOI：
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发表时间：
2014
影响因子：
4.2
通讯作者：
J. Abdenur
中科院分区：
文献类型：
--
作者：
Raymond Y. Wang;E. Monuki;J. Powers;Phillip H. Schwartz;P. Watkins;Yang Shi;A. Moser;D. Shrier;H. Waterham;D. Nugent;J. Abdenur
乙酰辅酶A氧化酶（ACOX1）缺乏症是一种罕见的过氧化物酶体极长链脂肪酸氧化障碍。没有详细描述尝试治疗、纵向成像或神经病理学的报告。我们描述的自然历史的临床症状和脑成像在两个兄弟姐妹ACOX1缺乏症，包括弟弟妹妹的反应异基因无关供体造血干细胞transplantation（HSCT）。MethodsWe进行了回顾性图表审查，以获得临床病史，神经影像学和神经病理学数据。进行ACOX1基因分型以确认疾病。在体外成纤维细胞和神经干细胞脂肪酸氧化测定也performed.ResultsBoth患者经历了致命的神经退行性过程中，晚期小脑和大脑灰质萎缩。弟弟的连续脑磁共振成像表明脱髓鞘开始于髓质，并向喙部进展，包括小脑、脑桥脑、中脑的白色物质，最终是皮质下白色物质。与未治疗的姐姐相比，成功植入的弟弟妹妹在神经成像和神经病理学上具有较少的脑炎症、皮质萎缩和神经元损失。成纤维细胞和干细胞表现出缺乏非常长链脂肪酸oxidation.InterpretationAlthough HSCT没有停止ACOX1缺乏的过程中，它减少了白色物质炎症在大脑中的程度。由于持续的神经元损失，脱髓鞘持续存在，这可能是由于移植无法防止灰质疾病的进展，长期使用皮质类固醇控制移植物抗宿主病的不良反应，或超过治疗疗效临界点的干预。
ObjectiveAcyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, including the younger sibling’s response to allogeneic unrelated donor hematopoietic stem cell transplantation (HSCT).MethodsWe conducted retrospective chart review to obtain clinical history, neuro-imaging, and neuropathology data. ACOX1 genotyping were performed to confirm the disease. In vitro fibroblast and neural stem cell fatty acid oxidation assays were also performed.ResultsBoth patients experienced a fatal neurodegenerative course, with late-stage cerebellar and cerebral gray matter atrophy. Serial brain magnetic resonance imaging in the younger sibling indicated demyelination began in the medulla and progressed rostrally to include the white matter of the cerebellum, pons, midbrain, and eventually subcortical white matter. The successfully engrafted younger sibling had less brain inflammation, cortical atrophy, and neuronal loss on neuro-imaging and neuropathology compared to the untreated older sister. Fibroblasts and stem cells demonstrated deficient very long chain fatty acid oxidation.InterpretationAlthough HSCT did not halt the course of ACOX1 deficiency, it reduced the extent of white matter inflammation in the brain. Demyelination continued because of ongoing neuronal loss, which may be due to inability of transplant to prevent progression of gray matter disease, adverse effects of chronic corticosteroid use to control graft-versus-host disease, or intervention occurring beyond a critical point for therapeutic efficacy.
DOI：
10.1002/ajmg.1320540108
发表时间：
1994-03-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
PULVER, AE;KARAYIORGOU, M;CHILDS, B
通讯作者：
CHILDS, B
胎儿肾上腺脑白质营养不良：肾上腺和睾丸病理病变的意义。
影响因子：
3.3
作者：
Powers,JM;Moser,HW;Moser,AB;Schaumburg,HH
通讯作者：
Schaumburg,HH