Reischl-Hajiabadi Anna T, Garbade Sven F, Gleich Florian, Schnabel-Besson Elena, Posset Roland, Zielonka Matthias, Hoffmann Georg F, Kölker Stefan, Mütze Ulrike
Medical Faculty of Heidelberg, Department of Pediatrics I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg University, Heidelberg, Germany.
J Inherit Metab Dis. 2025 Nov;48(6):e70090. doi: 10.1002/jimd.70090.
Classic isovaleric aciduria (cIVA) is a rare inherited metabolic disorder characterized by recurrent life-threatening metabolic decompensations and neurocognitive impairment in untreated patients. This meta-analysis aims to assess the impact of early diagnosis by newborn screening (NBS) on mortality and neurocognitive outcome. A systematic literature search for articles published until 2022 was conducted following PRISMA protocol guidelines. We investigated effects on clinical outcomes and survival, analyzing outcome parameters using meta-analytical measures and estimating effect sizes with a random-effects model. Overall, 20 studies were included, reporting on 240 individuals with cIVA. Individuals identified by NBS presented with a lower frequency of neurological symptoms (13.0% vs. 44.9%; p = 0.0040) and developmental delay (6.1% vs. 51.2%; p < 0.0001), and had a lower mortality rate (1.1% vs. 10.9%; p = 0.0320). The quality of healthcare systems did not have a measurable impact on neurocognitive outcome and mortality. Despite the beneficial effect of NBS on clinical outcome and mortality, it could not reliably prevent the manifestation of neonatal decompensation in all individuals with cIVA identified by NBS. Early diagnosis through NBS is essential for the timely initiation of therapy and for improving outcomes and survival rates in individuals with cIVA.
经典型异戊酸血症（cIVA）是一种罕见的遗传性代谢紊乱疾病，其特征是未经治疗的患者会反复出现危及生命的代谢失代偿和神经认知障碍。本荟萃分析旨在评估新生儿筛查（NBS）早期诊断对死亡率和神经认知结局的影响。按照PRISMA协议指南，对截至2022年发表的文章进行了系统的文献检索。我们研究了对临床结局和生存的影响，使用荟萃分析方法分析结局参数，并采用随机效应模型估计效应大小。总体而言，纳入了20项研究，报告了240例cIVA患者。通过NBS确诊的个体出现神经症状的频率较低（13.0%对44.9%；p = 0.0040）和发育迟缓的频率较低（6.1%对51.2%；p < 0.0001），死亡率也较低（1.1%对10.9%；p = 0.0320）。医疗保健系统的质量对神经认知结局和死亡率没有可测量的影响。尽管NBS对临床结局和死亡率有有益影响，但它不能可靠地预防所有通过NBS确诊的cIVA个体出现新生儿失代偿。通过NBS进行早期诊断对于及时开始治疗以及改善cIVA患者的结局和生存率至关重要。
