Newborn screening and disease variants predict neurological outcome in isovaleric aciduria

Journal of Inherited Metabolic Disease ◽

10.1002/jimd.12364 ◽

2021 ◽

Author(s):

Ulrike Mütze ◽

Lucy Henze ◽

Florian Gleich ◽

Martin Lindner ◽

Sarah C. Grünert ◽

...

Keyword(s):

Newborn Screening ◽

Neurological Outcome ◽

Isovaleric Aciduria

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Impact of newborn screening and quality of therapy on the neurological outcome in glutaric aciduria type 1: a meta-analysis

Genetics in Medicine ◽

10.1038/s41436-020-00971-4 ◽

2020 ◽

Vol 23 (1) ◽

pp. 13-21 ◽

Cited By ~ 1

Author(s):

Nikolas Boy ◽

Katharina Mengler ◽

Jana Heringer-Seifert ◽

Georg F. Hoffmann ◽

Sven F. Garbade ◽

...

Keyword(s):

Newborn Screening ◽

Motor Development ◽

Neurological Outcome ◽

Meta Analysis ◽

Glutaric Aciduria Type ◽

Glutaric Aciduria Type 1 ◽

Glutaric Aciduria ◽

Quality Of Therapy

Abstract Purpose Glutaric aciduria type 1 (GA1), a rare inherited neurometabolic disorder, results in a complex movement disorder (MD) with predominant dystonia if untreated. Implementation into newborn screening (NBS) programs and adherence to recommended therapy are thought to improve the neurological outcome. Methods Systematic literature search for articles published from 2000 to 2019 was performed using the PRISMA protocol. Studies reporting on more than one individual identified by NBS were included. We investigated effects of interventional and noninterventional variables on neurological outcome. Results Fifteen publications reporting on 647 GA1 patients were included. In the NBS group (n = 261 patients), 195 patients remained asymptomatic (74.7%), while 66 patients (25.3%) developed a MD. Compared with the NBS group, a much higher proportion of patients (349/386; 90.4%; p < 0.0001) diagnosed after the manifestation of neurologic symptoms had a MD and an abnormal motor development (285/349; 81.7%; p < 0.0001). For NBS patients, deviations from the recommended diet increased the risk of insidious onset MD, while delayed start of emergency treatment increased the risk of acute onset MD. Conclusions This meta-analysis demonstrates that NBS programs for GA1 have an overall positive effect on the neurological outcome of affected individuals but their success critically depends on the quality of therapy.

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