Abstract
Objectives: Metachromatic leukodystrophy (MLD) is a fatal lysosomal storage disease characterized by progressive demyelination within the central and peripheral nervous system. Rapid diagnosis is crucial in view of evolving therapeutic options. Strabismus has anecdotally been described as a feature in children with MLD. Our first aim was to examine the prevalence of strabismus as an early or even presenting sign of MLD in two nationwide cohorts. Second, we aimed to investigate the temporal relation between the onset of strabismus and gross motor deterioration, other early onset eye movement disorders and brain white matter abnormalities. Methods: Clinical records of 204 MLD patients at the University Children's Hospital Tubingen and Amsterdam University Medical Center were reviewed on the presence of strabismus and other eye movement disorders. Gross motor deterioration and white matter abnormalities on brain MRI were evaluated by using the Gross Motor Function Classification in MLD and MLD LOES score, respectively. Results: We identified strabismus as an early sign in MLD patients with the late-infantile form, with a prevalence of 27% (N = 17). The onset of strabismus preceded gross motor symptoms and brain white matter abnormalities in 71% and 46% respectively of the cases. Important characteristics were an acute-onset paralytic esotropia, partly accompanied by other eye movement abnormalities, and gadolinium enhancement of the cranial nerves. Conclusions: Acute-onset paralytic strabismus in toddlers should be considered a potential early sign of late-infantile MLD and might result from early cranial nerve involvement. Brain MRI with gadolinium contrast may facilitate early diagnosis.
Original language | English |
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Pages (from-to) | 87-93 |
Number of pages | 7 |
Journal | European Journal of Paediatric Neurology |
Volume | 37 |
Early online date | 3 Feb 2022 |
DOIs | |
Publication status | Published - Mar 2022 |
Bibliographical note
Funding Information:This study was in part supported by the Dutch charity organization Metakids (Metakids: 2017-073 to NIW); the Deutsche Forschungsgemeinschaft (DFG: GR 4688/2-1S . Groeschel), and by the European Reference Network for Rare Neurological Disorders (ERN-RND) , which is partly co-funded by the European Union within the framework of the Third Health Programme “ERN-2016 - Framework Partnership Agreement 2017–2021. NIW, MSvdK, IK-M and SG are members of the ERN-RND, project ID 739510. The funding sources had no role in the design and reporting of the study or in the decision to submit the manuscript for publication.
Funding Information:
This study was in part supported by the Dutch charity organization Metakids (Metakids: 2017-073 to NIW); the Deutsche Forschungsgemeinschaft (DFG: GR 4688/2-1S. Groeschel), and by the European Reference Network for Rare Neurological Disorders (ERN-RND), which is partly co-funded by the European Union within the framework of the Third Health Programme ?ERN-2016 - Framework Partnership Agreement 2017?2021. NIW, MSvdK, IK-M and SG are members of the ERN-RND, project ID 739510. The funding sources had no role in the design and reporting of the study or in the decision to submit the manuscript for publication.
Publisher Copyright:
© 2022 The Authors
Funding
This study was in part supported by the Dutch charity organization Metakids (Metakids: 2017-073 to NIW); the Deutsche Forschungsgemeinschaft (DFG: GR 4688/2-1S . Groeschel), and by the European Reference Network for Rare Neurological Disorders (ERN-RND) , which is partly co-funded by the European Union within the framework of the Third Health Programme “ERN-2016 - Framework Partnership Agreement 2017–2021. NIW, MSvdK, IK-M and SG are members of the ERN-RND, project ID 739510. The funding sources had no role in the design and reporting of the study or in the decision to submit the manuscript for publication. This study was in part supported by the Dutch charity organization Metakids (Metakids: 2017-073 to NIW); the Deutsche Forschungsgemeinschaft (DFG: GR 4688/2-1S. Groeschel), and by the European Reference Network for Rare Neurological Disorders (ERN-RND), which is partly co-funded by the European Union within the framework of the Third Health Programme ?ERN-2016 - Framework Partnership Agreement 2017?2021. NIW, MSvdK, IK-M and SG are members of the ERN-RND, project ID 739510. The funding sources had no role in the design and reporting of the study or in the decision to submit the manuscript for publication.
Funders | Funder number |
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Dutch charity organization Metakids | 2017-073 |
ERN-RND | 739510 |
European Commission | ERN-2016 |
European Commission | |
Deutsche Forschungsgemeinschaft | GR 4688/2-1S |
Deutsche Forschungsgemeinschaft |
Keywords
- Arylsulfatase A deficiency
- Cellular therapies
- Cranial nerves
- Esotropia
- Lysosomal storage disorder