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.

Details

Title
The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study
Author
Charlotte, Märtner E M 1 ; Thimm, Eva 2 ; Guder Philipp 3 ; Schiergens, Katharina A 4 ; Rutsch, Frank 5 ; Roloff, Sylvia 6 ; Marquardt, Iris 7 ; Das, Anibh M 8 ; Freisinger, Peter 9 ; Grünert, Sarah C 10 ; Krämer Johannes 11 ; Baumgartner, Matthias R 12 ; Beblo Skadi 13 ; Haase, Claudia 14 ; Dieckmann, Andrea 15 ; Lindner, Martin 16 ; Näke, Andrea 17 ; Hoffmann, Georg F 1 ; Mühlhausen, Chris 18 ; Walter, Magdalena 1 ; Garbade, Sven F 1 ; Maier, Esther M 4 ; Kölker Stefan 1 ; Boy Nikolas 19 

 University Hospital Heidelberg, Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908) 
 Heinrich Heine University Düsseldorf, Division of Experimental Paediatrics and Metabolism, Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children’s Hospital, Düsseldorf, Germany (GRID:grid.411327.2) (ISNI:0000 0001 2176 9917) 
 University Medical Center Hamburg-Eppendorf, Children’s Hospital, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484) 
 Ludwig-Maximilians-University, Dr. Von Hauner Children’s Hospital, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X) 
 University Children’s Hospital Muenster, Department of General Paediatrics, Metabolic Diseases, Muenster, Germany (GRID:grid.16149.3b) (ISNI:0000 0004 0551 4246) 
 Center for Chronically Sick Children, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639) 
 Children’s Hospital Oldenburg, Department of Child Neurology, Oldenburg, Germany (GRID:grid.7468.d) 
 Hannover Medical School, Department of Paediatrics, Paediatric Metabolic Medicine, Hannover, Germany (GRID:grid.10423.34) (ISNI:0000 0000 9529 9877) 
 Children’s Hospital Reutlingen, Reutlingen, Germany (GRID:grid.488549.c) 
10  University of Freiburg, Faculty of Medicine, Department of General Paediatrics, Adolescent Medicine and Neonatology, Medical Centre, Freiburg, Germany (GRID:grid.5963.9) 
11  University of Ulm, Department of Pediatric Neurology and Inborn Errors of Metabolism, Children’s Hospital, Ulm, Germany (GRID:grid.6582.9) (ISNI:0000 0004 1936 9748) 
12  University Children’s Hospital Zurich, Division of Metabolism and Children’s Research Centre, Zurich, Switzerland (GRID:grid.412341.1) (ISNI:0000 0001 0726 4330) 
13  University of Leipzig, Department of Women and Child Health, Hospital for Children and Adolescents, Centre for Paediatric Research Leipzig (CPL), University Hospitals, Leipzig, Germany (GRID:grid.9647.c) (ISNI:0000 0004 7669 9786) 
14  Helios Klinikum, Department of Pediatrics, Erfurt, Germany (GRID:grid.491867.5) (ISNI:0000 0000 9463 8339) 
15  Jena University Hospital, Centre for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena, Germany (GRID:grid.275559.9) (ISNI:0000 0000 8517 6224) 
16  University Children’s Hospital Frankfurt, Division of Paediatric Neurology, Frankfurt, Germany (GRID:grid.410607.4) 
17  Technical University, Children’s Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.4488.0) (ISNI:0000 0001 2111 7257) 
18  University Medical Center, Department of Pediatrics and Adolescent Medicine, Göttingen, Germany (GRID:grid.411984.1) (ISNI:0000 0001 0482 5331) 
19  University Hospital Heidelberg, Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908); University Hospital Heidelberg, Division of Paediatric Neurology and Metabolic Medicine, Department of General Paediatrics, Centre for Paediatrics and Adolescent Medicine, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2577604993
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.