Neuropediatrics 2021; 52(S 01): S1-S53
DOI: 10.1055/s-0041-1739688
Freier Vortrag

The Biochemical High Excreter Phenotype Is the Major Risk Factor for Cognitive Impairment in Early Diagnosed Individuals with Glutaric Aciduria Type 1

E. M. Charlotte Märtner
1   Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Germany
,
Eva Thimm
2   Division of Experimental Paediatrics and Metabolism, Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Philipp Guder
3   Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Katharina A. Schiergens
4   Dr. von Hauner Children's Hospital, Ludwig-Maximilian University, Munich, Germany
,
Frank Rutsch
5   Department of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Muenster, Germany
,
Sylvia Roloff
6   Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Chronically Sick Children, Berlin, Germany
,
Iris Marquardt
7   Department of Child Neurology, Children's Hospital Oldenburg, Oldenburg, Germany
,
Anibh M. Das
8   Department of Paediatrics, Paediatric Metabolic Medicine, Hannover Medical School, Hannover, Germany
,
Peter Freisinger
9   Children's Hospital Reutlingen, Reutlingen, Germany
,
Sarah C. Grünert
10   Department of General Paediatrics, Adolescent Medicine and Neonatology, Medical Centre, University of Freiburg, Faculty of Medicine, Freiburg, Germany
,
Johannes Krämer
11   Department of Pediatric Neurology and Inborn Errors of Metabolism, Children's Hospital, University of Ulm, Ulm, Germany
,
Matthias R. Baumgartner
12   Division of Metabolism and Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland
,
Skadi Beblo
13   Department of Women and Child Health, Hospital for Children and Adolescents, Centre for Paediatric Research Leipzig (CPL), University Hospitals, University of Leipzig, Leipzig, Germany
,
Claudia Haase
14   Department of Pediatrics, Helios Klinikum Erfurt, Germany
,
Andrea Dieckmann
15   Centre for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena, Germany
,
Martin Lindner
16   Division of Paediatric Neurology, University Children's Hospital Frankfurt, Frankfurt, Germany
,
Andrea Näke
17   Children's Hospital Carl Gustav Carus, Technical University Dresden, Germany
,
Georg F. Hoffmann
1   Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Germany
,
Chris Mühlhausen
18   Department of Pediatrics and Adolescent Medicine, University Medical Center, Gottingen, Germany
,
Magdalena Walter
1   Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Germany
,
Sven F. Garbade
1   Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Germany
,
Esther M. Maier
4   Dr. von Hauner Children's Hospital, Ludwig-Maximilian University, Munich, Germany
,
Stefan Kölker
1   Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Germany
,
Nikolas Boy
1   Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Germany
› Author Affiliations
› Further Information
 

Background: Glutaric aciduria type 1 (GA1) is a rare inherited neurometabolic disorder. Both biochemical subtypes, i.e., high and low excreter share the same risk for severe movement disorder if untreated. Implementation into national newborn screening programs dramatically improved neurologic outcome, but cognitive functions have not systematically been studied.

Methods: This national prospective observational study includes 107 individuals with confirmed GA1 identified by newborn screening between 1999 and 2020 in Germany. Standardized cognitive tests were used to evaluate clinical and cognitive (development and IQ) outcome.

Results: Median age of 72 patients with at least one cognitive test was 7.9 years. Global development was normal in the majority of younger patients (15 of 24 [63%]; age range: 0.6–5.6 years). Isolated or global deficits were more frequent in patients with movement disorder (7 of 9 patients [78%]). Older patients with IQ tests (n = 56; age range: 3.4–19.1) showed significantly lower results than general population (median IQ: 87; interquartile range [IQR]: 78–98) which was more pronounced in individuals with high excreter phenotype (median IQ: 84; IQR: 75–96) than in low excreter patients (median IQ: 98; IQR: 92–105; p = 0.0164). Results were stable with age and homogenous on subscale level. Cognitive outcome was not impacted by sex, motor function, and quality of metabolic treatment.

Conclusion: In GA1, neurologic long-term impairment involves both motor and cognitive function. Cognition is impacted by biochemical phenotype, but not by current therapy and striatal damage, implicating the necessity of more effective long-term treatment concepts, especially for high excreting patients.



Publication History

Article published online:
28 October 2021

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