The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study

Abstract The aim of the study was a systematic evaluation of cognitive development in individuals with glutaric aciduria type 1 (GA1), a rare neurometabolic disorder, identified by newborn screening in Germany. This national, prospective, observational, multi-centre study includes 107 individuals wi...

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Autores principales:	E. M. Charlotte Märtner, Eva Thimm, Philipp Guder, Katharina A. Schiergens, Frank Rutsch, Sylvia Roloff, Iris Marquardt, Anibh M. Das, Peter Freisinger, Sarah C. Grünert, Johannes Krämer, Matthias R. Baumgartner, Skadi Beblo, Claudia Haase, Andrea Dieckmann, Martin Lindner, Andrea Näke, Georg F. Hoffmann, Chris Mühlhausen, Magdalena Walter, Sven F. Garbade, Esther M. Maier, Stefan Kölker, Nikolas Boy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da32808a76694de6ae0aa2dc357545d7
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spelling	oai:doaj.org-article:da32808a76694de6ae0aa2dc357545d72021-12-02T18:51:14ZThe biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study10.1038/s41598-021-98809-92045-2322https://doaj.org/article/da32808a76694de6ae0aa2dc357545d72021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98809-9https://doaj.org/toc/2045-2322Abstract The aim of the study was a systematic evaluation of cognitive development in individuals with glutaric aciduria type 1 (GA1), a rare neurometabolic disorder, identified by newborn screening in Germany. This national, prospective, observational, multi-centre study includes 107 individuals with confirmed GA1 identified by newborn screening between 1999 and 2020 in Germany. Clinical status, development, and IQ were assessed using standardized tests. Impact of interventional and non-interventional parameters on cognitive outcome was evaluated. The majority of tested individuals (n = 72) showed stable IQ values with age (n = 56 with IQ test; median test age 11 years) but a significantly lower performance (median [IQR] IQ 87 [78–98]) than in general population, particularly in individuals with a biochemical high excreter phenotype (84 [75–96]) compared to the low excreter group (98 [92–105]; p = 0.0164). For all patients, IQ results were homogenous on subscale levels. Sex, clinical motor phenotype and quality of metabolic treatment had no impact on cognitive functions. Long-term neurologic outcome in GA1 involves both motor and cognitive functions. The biochemical high excreter phenotype is the major risk factor for cognitive impairment while cognitive functions do not appear to be impacted by current therapy and striatal damage. These findings implicate the necessity of new treatment concepts.E. M. Charlotte MärtnerEva ThimmPhilipp GuderKatharina A. SchiergensFrank RutschSylvia RoloffIris MarquardtAnibh M. DasPeter FreisingerSarah C. GrünertJohannes KrämerMatthias R. BaumgartnerSkadi BebloClaudia HaaseAndrea DieckmannMartin LindnerAndrea NäkeGeorg F. HoffmannChris MühlhausenMagdalena WalterSven F. GarbadeEsther M. MaierStefan KölkerNikolas BoyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q E. M. Charlotte Märtner Eva Thimm Philipp Guder Katharina A. Schiergens Frank Rutsch Sylvia Roloff Iris Marquardt Anibh M. Das Peter Freisinger Sarah C. Grünert Johannes Krämer Matthias R. Baumgartner Skadi Beblo Claudia Haase Andrea Dieckmann Martin Lindner Andrea Näke Georg F. Hoffmann Chris Mühlhausen Magdalena Walter Sven F. Garbade Esther M. Maier Stefan Kölker Nikolas Boy The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
description	Abstract The aim of the study was a systematic evaluation of cognitive development in individuals with glutaric aciduria type 1 (GA1), a rare neurometabolic disorder, identified by newborn screening in Germany. This national, prospective, observational, multi-centre study includes 107 individuals with confirmed GA1 identified by newborn screening between 1999 and 2020 in Germany. Clinical status, development, and IQ were assessed using standardized tests. Impact of interventional and non-interventional parameters on cognitive outcome was evaluated. The majority of tested individuals (n = 72) showed stable IQ values with age (n = 56 with IQ test; median test age 11 years) but a significantly lower performance (median [IQR] IQ 87 [78–98]) than in general population, particularly in individuals with a biochemical high excreter phenotype (84 [75–96]) compared to the low excreter group (98 [92–105]; p = 0.0164). For all patients, IQ results were homogenous on subscale levels. Sex, clinical motor phenotype and quality of metabolic treatment had no impact on cognitive functions. Long-term neurologic outcome in GA1 involves both motor and cognitive functions. The biochemical high excreter phenotype is the major risk factor for cognitive impairment while cognitive functions do not appear to be impacted by current therapy and striatal damage. These findings implicate the necessity of new treatment concepts.
format	article
author	E. M. Charlotte Märtner Eva Thimm Philipp Guder Katharina A. Schiergens Frank Rutsch Sylvia Roloff Iris Marquardt Anibh M. Das Peter Freisinger Sarah C. Grünert Johannes Krämer Matthias R. Baumgartner Skadi Beblo Claudia Haase Andrea Dieckmann Martin Lindner Andrea Näke Georg F. Hoffmann Chris Mühlhausen Magdalena Walter Sven F. Garbade Esther M. Maier Stefan Kölker Nikolas Boy
author_facet	E. M. Charlotte Märtner Eva Thimm Philipp Guder Katharina A. Schiergens Frank Rutsch Sylvia Roloff Iris Marquardt Anibh M. Das Peter Freisinger Sarah C. Grünert Johannes Krämer Matthias R. Baumgartner Skadi Beblo Claudia Haase Andrea Dieckmann Martin Lindner Andrea Näke Georg F. Hoffmann Chris Mühlhausen Magdalena Walter Sven F. Garbade Esther M. Maier Stefan Kölker Nikolas Boy
author_sort	E. M. Charlotte Märtner
title	The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
title_short	The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
title_full	The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
title_fullStr	The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
title_full_unstemmed	The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
title_sort	biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da32808a76694de6ae0aa2dc357545d7
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The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study

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