Genet Med. 2024 Oct 17:101303. doi: 10.1016/j.gim.2024.101303. Online ahead of print.
ABSTRACT
PURPOSE: Maple syrup urine disease (MSUD) is a rare inherited metabolic disease characterised 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 healthcare systems.
METHODS: Systematic literature search was performed according to PRISMA-P. Effects on outcome parameters were analysed using meta-analytical measures and re-analysis of individual participant data.
RESULTS: Thirty-three studies were included, reporting on 1141 individuals with MSUD. Participants with classic MSUD presented a more severe phenotype compared to 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 to individuals identified after onset of symptoms, in trend even after exclusion of individuals with variant MSUD. Quality of national healthcare systems correlated with survival (P=.025, meta-regression) and permanent neurological symptoms (P=.031, meta-regression).
CONCLUSION: NBS is a prerequisite to improved outcome in individuals with MSUD; however, health benefit critically depends on the quality of the national healthcare systems.
PMID:39431354 | DOI:10.1016/j.gim.2024.101303
