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Published on: October 21, 2014
A model of neuronopathic Gaucher disease
P E Campbell1, C M Harris, C M Harris
1Department of Audiological Medicine, Great Ormond Street Hospital for Children, London. pauline.campbell@plymouth.ac.uk
Journal of Inherited Metabolic Disease
|January 7, 2004
Summary
Enzyme replacement therapy (ERT) showed limited efficacy in neuronopathic Gaucher disease (NGD). Infants with NGD experienced relentless neurological decline despite high-dose ERT, suggesting excitotoxic damage as a potential therapeutic target.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebroside accumulation.
- Neuronopathic Gaucher disease (NGD) involves systemic and neurological manifestations, with limited treatment options.
- Enzyme replacement therapy (ERT) is effective for systemic GD but less so for NGD.
Observation:
- Two infants with NGD presented with bulbar palsy and failure to thrive.
- High-dose ERT was administered, but biochemical markers showed an incomplete systemic response.
- Neurological deterioration was relentless, leading to death in both infants.
Findings:
- Oculomotor assessment revealed absent saccadic eye movements and sixth nerve palsy.
- Audiological assessment showed progressive auditory brain stem response (ABR) deterioration with preserved peripheral hearing.
- This pattern suggests inner hair cell pathway dysfunction, akin to auditory neuropathy.
Implications:
- The findings suggest an excitotoxic mechanism contributing to NGD neurodegeneration.
- Glucocerebroside toxicity may be exacerbated by excitotoxicity.
- Targeting excitotoxic damage presents a potential therapeutic avenue for NGD.
