Haematopoietic stem cell transplantation does not retard disease progression in the psycho-cognitive variant of late-onset metachromatic leukodystrophy
Haematopoietic stem cell transplantation does not retard disease progression in the psycho-cognitive variant of late-onset metachromatic leukodystrophy
复制标题
造血干细胞移植不会延缓迟发性异染性脑白质营养不良心理认知变异型的疾病进展
DOI：
10.1007/s10545-010-9240-1
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发表时间：
2010
影响因子：
4.2
通讯作者：
T. Cox
中科院分区：
文献类型：
--
作者：
N. Smith;R. Marcus;B. Sahakian;N. Kapur;T. Cox
造血干细胞移植在治疗迟发性异染性脑白质营养不良中的作用尚未得到证实：理论上通过植入充满酶的造血祖细胞和通过酶重捕获恢复神经组织中的硫苷脂代谢能力得到证实，但长期结果尚不清楚。罕见的心理认知变异和迟发性疾病的缓慢进展损害了治疗的评价。我们报告了一个迟发性异染性脑白质营养不良患者造血干细胞移植后详细的临床和神经心理学评估。认知能力下降，无法区分的自然病程的疾病，连续记录超过11年，尽管完整的供体嵌合体和校正白细胞芳基硫酸酯酶A野生型值;微妙的运动退化同样注意到和进行性脑容量损失是明显的磁共振成像。感觉神经传导在移植后17个月恶化，在11年回顾时明显稳定。造血干细胞移植对这种罕见的异染性脑白质营养不良的减毒变异无效。在少数患者中，缺乏明确的建议;当考虑移植时，来自酶充满供体的脐带血移植物与来自同一来源的连续性间充质干细胞输注可能是优选的。改善的结果将取决于提高对疾病的认识和早期诊断，以便有希望的干预措施，如转基因、自体干细胞移植，有最好的成功机会。
Haematopoietic stem cell transplantation has an unproven role in the management of late-onset metachromatic leukodystrophy: theoretically justified through the engraftment of enzyme-replete haematopoietic progenitors and restoration of capacity for sulphatide catabolism in neural tissue through enzyme recapture, the long-term outcome is unknown. The rarity of the psycho-cognitive variant and slow progression of late-onset disease impairs evaluation of treatment. We report detailed clinical and neuropsychological assessments after haematopoietic stem-cell transplantation in a patient with a late-onset psycho-cognitive form of metachromatic leukodystrophy. Cognitive decline, indistinguishable from the natural course of the disease, was serially documented over 11 years despite complete donor chimaerism and correction of leukocyte arylsulphatase A to wild type values; subtle motor deterioration was similarly noted and progressive cerebral volume loss was evident upon magnetic resonance imaging. Sensory nerve conduction deteriorated 17 months post-transplantation with apparent stabilisation at 11-year review. Haematopoietic stem-cell transplantation was ineffective for this rare attenuated variant of metachromatic leukodystrophy. In the few patients identified pre-symptomatically or with early-phase disease, clear recommendations are lacking; when transplantation is considered, umbilical cord blood grafts from enzyme-replete donors with adjunctive mesenchymal stem cell infusions from the same source may be preferable. Improved outcomes will depend on enhanced awareness and early diagnosis of the disease, so that promising interventions such as genetically modified, autologous stem cell transplantation have the best opportunity of success.