Department of Child Neurology, Center for Children with White Matter Disorders, VU Medical Centre and Neuroscience Campus, Postbox 7057, 1007 MB Amsterdam, The Netherlands.
Department of Pediatrics, Blood and Marrow Transplantation Program, University Medical Center Utrecht, PO Box 85090, 3503 AB Utrecht, The Netherlands.
Best Pract Res Clin Endocrinol Metab. 2015 Mar;29(2):261-73. doi: 10.1016/j.beem.2014.10.001. Epub 2014 Oct 16.
Metachromatic leukodystrophy is an inherited lysosomal disorder caused by recessive mutations in ARSA encoding arylsulfatase A. Low activity of arylsulfatase A results in the accumulation of sulfatides in the central and peripheral nervous system leading to demyelination. The disease is classified in a late-infantile, juvenile and adult onset type based on the age of onset, all characterized by a variety of neurological symptoms, which eventually lead to death if untreated. There is no curative treatment for all types and stages. This review discusses diagnostic process and efficacy of current and possible future therapies such as hematopoietic stem cell transplantation, enzyme replacement therapy and gene therapy. A systematic evaluation regarding the efficacy of hematopoietic stem cell transplantation and a longer follow up period for gene therapy are needed to come to a general conclusion and improve treatment options for metachromatic leukodystrophy.
异染性脑白质营养不良是一种遗传性溶酶体疾病,由 ARSA 编码的芳基硫酸酯酶 A 的隐性突变引起。芳基硫酸酯酶 A 的活性降低导致硫酸脂在中枢和周围神经系统中积累,导致脱髓鞘。根据发病年龄,该疾病可分为晚发性婴儿型、少年型和成人型,所有类型均以多种神经症状为特征,如果不治疗,最终会导致死亡。所有类型和阶段均无治愈方法。本文综述了目前和可能的未来治疗方法,如造血干细胞移植、酶替代疗法和基因疗法的诊断过程和疗效。需要对造血干细胞移植的疗效进行系统评估,并对基因治疗进行更长时间的随访,以得出一般结论并改善异染性脑白质营养不良的治疗选择。