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Patterns, evolution, and severity of striatal injury in insidious- versus acute-onset glutaric aciduria type 1

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Background

Striatal injury in patients with glutaric aciduria type 1 (GA1) results in a complex, predominantly dystonic, movement disorder. Onset may be acute following acute encephalopathic crisis (AEC) or insidious without apparent acute event.

Methods

We analyzed clinical and striatal magnetic resonance imaging (MRI) findings in 21 symptomatic GA1 patients to investigate if insidious- and acute-onset patients differed in timing, pattern of striatal injury, and outcome.

Results

Eleven patients had acute and ten had insidious onset, two with later AEC (acute-on-insidious). The median onset of dystonia was 10 months in both groups, and severity was greater in patients after AEC (n = 8 severe, n = 5 moderate) than in insidious onset (n = 4 mild, n = 3 moderate, n = 1 severe). Deviations from guideline-recommended basic metabolic treatment were identified in six insidious-onset patients. Striatal lesions were extensive in all acute-onset patients and restricted to the dorsolateral putamen in eight of ten insidious-onset patients. After AEC, the two acute-on-insidious patients had extensive striatal changes superimposed on pre-existing dorsolateral putaminal lesions. Two insidious-onset patients with progressive dystonia without overt AEC also had extensive striatal changes, one with sequential striatal injury revealed by diffusion-weighted imaging. Insidious-onset patients had a latency phase of 3.5 months to 6.5 years between detection and clinical manifestation of dorsolateral putaminal lesions.

Conclusions

Insidious-onset type GA1 is characterized by dorsolateral putaminal lesions, less severe dystonia, and an asymptomatic latency phase, despite already existing lesions. Initially normal MRI during the first months and deviations from guideline-recommended treatment in a large proportion of insidious-onset patients substantiate the protective effect of neonatally initiated treatment.

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Acknowledgements

We thank the patients and their parents for their support and participation in this study.

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Authors and Affiliations

  1. Centre for Child and Adolescent Medicine, Clinic I, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Nikolas Boy, Sven F. Garbade, Jana Heringer & Stefan Kölker

  2. Department of Neuroradiology, University of Heidelberg Medical Center, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Angelika Seitz & Inga Harting

Authors
  1. Nikolas Boy
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  2. Sven F. Garbade
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  3. Jana Heringer
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  4. Angelika Seitz
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  5. Stefan Kölker
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  6. Inga Harting
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Corresponding author

Correspondence to Inga Harting.

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Conflict of interest

N. Boy, S. F. Garbade, J. Heringer, A. Seitz, and I. Harting declare that they have no conflict of interest.

S. Kölker received funding from the European Union via Chafea, in the framework of the Health Programme, for the project “European registry and network for intoxication type metabolic diseases” (E-IMD; grant no. 2010 12 01). The author confirms independence from the sponsors; the content of the article has not been influenced by the sponsors.

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Communicated by: Jerry Vockley

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Boy, N., Garbade, S.F., Heringer, J. et al. Patterns, evolution, and severity of striatal injury in insidious- versus acute-onset glutaric aciduria type 1. J Inherit Metab Dis (2018). https://doi.org/10.1007/s10545-018-0187-y

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  • DOI: https://doi.org/10.1007/s10545-018-0187-y

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