背景:异染性脑白质营养不良(MLD)是一种常染色体隐性遗传性溶酶体贮积病,由主要由ASA基因(ARSA)变异体引起的芳基硫酸酯酶A(ASA)活性缺乏引起。晚期婴儿,青少年和成人临床亚型的定义为症状发作在≤2.5,>2.5至<16和≥16岁,分别。寻求流行病学数据以解决知识空白并为有关研究药物临床开发的决策提供信息。
方法:综合全世界和选定国家的MLD发病率和出生患病率的所有可用估计,OvidMEDLINE和Embase进行了系统搜索(2022年3月11日),干预,比较器,结果,时间和设置框架,辅之以语用搜索,以减少出版偏见。在可能的情况下,结果按临床亚型分层。数据来自非干预研究(临床试验,非临床研究和病例报告被排除;综述仅用于滚雪球).
结果:在纳入的31项研究中,14个报告的出生流行率(亚太地区13个国家,欧洲,中东,北美和南美),1例报告患病率,无1例报告发病率.每100,000名活产婴儿的出生患病率为0.16(日本)至1.85(葡萄牙)。在三项按临床亚型分层估计的欧洲研究中,晚期婴儿病例的出生患病率最高(每100,000例活产0.31-1.12).在17项研究中,在不同时间段诊断的病例中报告的临床亚型分布差异很大,但是在大多数研究中,晚期婴儿和青少年MLD至少占病例的三分之二。
结论:本综述为进一步分析MLD的区域流行病学奠定了基础。数据缺口表明需要更好地覆盖全球,增加流行病学措施的使用(例如患病率估计)和更多的临床和遗传疾病亚型的结果分层.
BACKGROUND: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. Late-infantile, juvenile and adult clinical subtypes are defined by symptom onset at ≤ 2.5, > 2.5 to < 16 and ≥ 16 years, respectively. Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug.
METHODS: To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. Where possible, results were stratified by clinical subtype. Data were extracted from non-interventional studies (clinical trials, non-clinical studies and case reports were excluded; reviews were used for snowballing only).
RESULTS: Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia-Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal). In the three European studies with estimates stratified by clinical subtypes, birth prevalence was highest for late-infantile cases (0.31-1.12 per 100,000 live births). The distribution of clinical subtypes reported in cases diagnosed over various time periods in 17 studies varied substantially, but late-infantile and juvenile MLD accounted for at least two-thirds of cases in most studies.
CONCLUSIONS: This review provides a foundation for further analysis of the regional epidemiology of MLD. Data gaps indicate the need for better global coverage, increased use of epidemiological measures (e.g. prevalence estimates) and more stratification of outcomes by clinical and genetic disease subtype.