Takeda Development Center Americas, Inc., 125 Binney Street, Cambridge, MA, USA.
Oxford PharmaGenesis, Oxford, UK.
Eur J Med Res. 2024 Mar 18;29(1):181. doi: 10.1186/s40001-024-01771-1.
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.
黏脂贮积症（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 活性缺乏引起，导致神经组织中硫酸脂的积累。本系统文献综述旨在探讨 MLD 对患者生活的影响。
使用 Ovid 平台检索 Embase、MEDLINE 和 Cochrane 图书馆中与 MLD 的自然史、临床结局和疾病负担相关的文章；使用“黏脂贮积症”作为关键词进行会议和手工检索。在确定的 531 篇出版物中，经过筛选后有 120 篇被纳入数据提取。这里呈现了与 MLD 自然史和疾病负担相关的研究的一部分发现（n=108）。
晚发性婴儿型 MLD 的症状发作平均年龄一般为 16-18 个月，少年型 MLD 的平均年龄为 6-10 岁。诊断年龄和诊断时间差异很大。通常，晚发性婴儿型 MLD 患者主要表现为运动症状和发育迟缓；少年型 MLD 患者表现为运动、认知和行为症状；成年型 MLD 患者表现为认知症状和精神和情绪障碍。晚发性婴儿型 MLD 患者的运动功能随时间的推移下降更快，生存率低于少年型 MLD 患者。常见的合并症/并发症包括共济失调、癫痫、胆囊异常、尿失禁、神经病和癫痫发作。
按地理区域划分的 MLD 流行病学、定量认知数据、早晚期少年型 MLD 之间的差异数据以及人文或经济结局数据有限。需要进一步研究临床、人文（即生活质量）和经济结局，以帮助为 MLD 患者的医疗保健决策提供信息。
