Header

UZH-Logo

Maintenance Infos

Impact of interventional and non‐interventional variables on anthropometric long‐term development in glutaric aciduria type 1: A national prospective multi‐centre study


Märtner, E M Charlotte; Maier, Esther M; Mengler, Katharina; Thimm, Eva; Schiergens, Katharina A; Marquardt, Thorsten; Santer, René; Weinhold, Natalie; Marquardt, Iris; Das, Anibh M; Freisinger, Peter; Grünert, Sarah C; Vossbeck, Judith; Steinfeld, Robert; Baumgartner, Matthias R; Beblo, Skadi; Dieckmann, Andrea; Näke, Andrea; Lindner, Martin; Heringer‐Seifert, Jana; Lenz, Dominic; Hoffmann, Georg F; Mühlhausen, Chris; Ensenauer, Regina; Garbade, Sven F; Kölker, Stefan; Boy, Nikolas (2020). Impact of interventional and non‐interventional variables on anthropometric long‐term development in glutaric aciduria type 1: A national prospective multi‐centre study. Journal of Inherited Metabolic Disease:Epub ahead of print.

Abstract

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder, caused by inherited deficiency of glutaryl-CoA dehydrogenase, mostly affecting the brain. Early identification by newborn screening (NBS) significantly improves neurologic outcome. It has remained unclear whether recommended therapy, particular low lysine diet, is safe or negatively affects anthropometric long-term outcome. This national prospective, observational, multi-centre study included 79 patients identified by NBS and investigated effects of interventional and non-interventional parameters on body weight, body length, body mass index (BMI) and head circumference as well as neurological parameters. Adherence to recommended maintenance and emergency treatment (ET) had a positive impact on neurologic outcome and allowed normal anthropometric development until adulthood. In contrast, non-adherence to ET, resulting in increased risk of dystonia, had a negative impact on body weight (mean SDS -1.07; P = .023) and body length (mean SDS -1.34; P = -.016). Consistently, longitudinal analysis showed a negative influence of severe dystonia on weight and length development over time (P < .001). Macrocephaly was more often found in female (mean SDS 0.56) than in male patients (mean SDS -0.20; P = .049), and also in individuals with high excreter phenotype (mean SDS 0.44) compared to low excreter patients (mean SDS -0.68; P = .016). In GA1, recommended long-term treatment is effective and allows for normal anthropometric long-term development up to adolescence, with gender- and excreter type-specific variations. Delayed ET and severe movement disorder result in poor anthropometric outcome.

Abstract

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder, caused by inherited deficiency of glutaryl-CoA dehydrogenase, mostly affecting the brain. Early identification by newborn screening (NBS) significantly improves neurologic outcome. It has remained unclear whether recommended therapy, particular low lysine diet, is safe or negatively affects anthropometric long-term outcome. This national prospective, observational, multi-centre study included 79 patients identified by NBS and investigated effects of interventional and non-interventional parameters on body weight, body length, body mass index (BMI) and head circumference as well as neurological parameters. Adherence to recommended maintenance and emergency treatment (ET) had a positive impact on neurologic outcome and allowed normal anthropometric development until adulthood. In contrast, non-adherence to ET, resulting in increased risk of dystonia, had a negative impact on body weight (mean SDS -1.07; P = .023) and body length (mean SDS -1.34; P = -.016). Consistently, longitudinal analysis showed a negative influence of severe dystonia on weight and length development over time (P < .001). Macrocephaly was more often found in female (mean SDS 0.56) than in male patients (mean SDS -0.20; P = .049), and also in individuals with high excreter phenotype (mean SDS 0.44) compared to low excreter patients (mean SDS -0.68; P = .016). In GA1, recommended long-term treatment is effective and allows for normal anthropometric long-term development up to adolescence, with gender- and excreter type-specific variations. Delayed ET and severe movement disorder result in poor anthropometric outcome.

Statistics

Citations

Altmetrics

Downloads

4 downloads since deposited on 13 Jan 2021
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Genetics
Health Sciences > Genetics (clinical)
Language:English
Date:2020
Deposited On:13 Jan 2021 16:49
Last Modified:14 Jan 2021 21:00
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0141-8955
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1002/jimd.12335

Download

Hybrid Open Access

Download PDF  'Impact of interventional and non‐interventional variables on anthropometric long‐term development in glutaric aciduria type 1: A national prospective multi‐centre study'.
Preview
Content: Published Version
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)