Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients. The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using ‘metachromatic leukodystrophy’ as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here. The mean age at symptom onset was generally 16–18 months for late-infantile MLD and 6–10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures. Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.

中文翻译：

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异染性脑白质营养不良的自然史和疾病负担：系统文献综述

异染性脑白质营养不良（MLD；OMIM 250100 和 249900）是一种罕见的溶酶体贮积病，由芳基硫酸酯酶 A 活性缺陷引起，导致脑硫苷脂在神经系统中积聚。本系统文献综述旨在探讨MLD对患者生活的影响。Ovid 平台用于搜索 Embase、MEDLINE 和 Cochrane 图书馆，查找与 MLD 自然史、临床结果和疾病负担相关的文章；使用“异染性脑白质营养不良”作为关键词进行国会和手工搜查。在确定的 531 篇出版物中，有 120 篇被纳入筛选后进行数据提取。这里介绍了与 MLD 自然史和疾病负担 (n = 108) 有关的研究结果的子集。晚期婴儿 MLD 的平均发病年龄一般为 16-18 个月，青少年 MLD 的平均发病年龄为 6-10 岁。诊断时的年龄和诊断时间差异很大。通常，婴儿晚期 MLD 患者主要表现为运动症状和发育迟缓；青少年 MLD 患者出现运动、认知和行为症状；成人 MLD 患者出现认知症状以及精神和情绪障碍。与青少年 MLD 患者相比，晚期婴儿 MLD 患者运动功能随时间下降更快，生存率更低。常见的合并症/并发症包括共济失调、癫痫、胆囊异常、失禁、神经病变和癫痫发作。按地理区域划分的 MLD 流行病学、定量认知数据、早期和晚期青少年 MLD 之间差异的数据以及人文或经济结果都很有限。需要对临床、人文（即生活质量）和经济结果进行进一步研究，以帮助为 MLD 患者做出医疗保健决策。