Scharre Svenja, Mengler Katharina, Schnabel Elena, Kuseyri Hübschmann Oya, Tuncel Ali Tunç, Hoffmann Georg Friedrich, Garbade Sven F, Mütze Ulrike, Kölker Stefan
Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department of Pediatrics I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany.
Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department of Pediatrics I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany.
Genet Med. 2025 Jan;27(1):101303. doi: 10.1016/j.gim.2024.101303. Epub 2024 Oct 18.
Maple syrup urine disease (MSUD) is a rare inherited metabolic disease characterized by recurrent metabolic decompensations, neurocognitive impairment, and limited life expectancy. This meta-analysis aims to evaluate the impact of early diagnosis by newborn screening (NBS) on mortality and neurocognitive outcome in survivors, taking into account the quality of national health care systems.
Systematic literature search was performed according to Preferred Reporting Items for Systematic Review and Meta-Analysis protocol. Effects on outcome parameters were analyzed using meta-analytical measures and reanalysis of individual participant data.
Thirty-three studies were included, reporting on 1141 individuals with MSUD. Participants with classic MSUD presented a more severe phenotype compared with variant MSUD as demonstrated by higher mortality rate (17.1% versus 0%), and lower median IQ (90 versus 104; P < .001, linear mixed model). NBS was associated with improved cognition (mean IQ: 95 versus 82; P = .014, random effects model) and decreased mortality (3% versus 14.6%; P = .028, Kaplan-Meier estimates) compared with individuals identified after onset of symptoms, in trend even after the exclusion of individuals with variant MSUD. Quality of national health care systems correlated with survival (P = .025, meta-regression) and permanent neurological symptoms (P = .031, meta-regression).
NBS is a prerequisite to improved outcome in individuals with MSUD; however, health benefit critically depends on the quality of the national health care systems.
枫糖尿症（MSUD）是一种罕见的遗传性代谢疾病，其特征为反复出现代谢失代偿、神经认知障碍以及预期寿命有限。本荟萃分析旨在评估新生儿筛查（NBS）早期诊断对幸存者死亡率和神经认知结局的影响，并考虑国家卫生保健系统的质量。
根据系统评价和荟萃分析的首选报告项目协议进行系统文献检索。使用荟萃分析方法和对个体参与者数据的重新分析来分析对结局参数的影响。
纳入了33项研究，报告了1141例MSUD患者。与变异型MSUD相比，经典型MSUD患者表现出更严重的表型，死亡率更高（17.1%对0%），中位数智商更低（90对104；P<.001，线性混合模型）。与症状出现后确诊的个体相比，NBS与认知改善（平均智商：95对82；P=.014，随机效应模型）和死亡率降低（3%对14.6%；P=.028，Kaplan-Meier估计）相关，即使在排除变异型MSUD个体后仍呈此趋势。国家卫生保健系统的质量与生存率（P=.025，荟萃回归）和永久性神经症状（P=.031，荟萃回归）相关。
NBS是改善MSUD患者结局的先决条件；然而，健康获益严重依赖于国家卫生保健系统的质量。
