Abstract
Among the phenotypes associated with Gaucher disease, the deficiency of glucocerebrosidase, are rare patients with early onset, treatment-refractory parkinsonism. Sequencing of glucocerebrosidase in 17 such patients revealed 12 different genotypes. Fourteen patients had the common "non-neuronopathic" N370S mutation, including five N370S homozygotes. While brain glucosylsphingosine levels were not elevated, Lewy bodies were seen in the four brains available for study. The shared clinical and neuropathologic findings in this subgroup suggest that the deficiency in glucocerebrosidase may contribute to a vulnerability to parkinsonism.
MeSH terms
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Adult
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Blotting, Southern
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Brain / metabolism
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Brain / pathology
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Deoxyribonucleases, Type II Site-Specific / genetics
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Female
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Gaucher Disease / complications
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Gaucher Disease / genetics*
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Gaucher Disease / metabolism
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Gaucher Disease / pathology
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Genetic Predisposition to Disease*
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Glucosylceramidase / deficiency*
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Glucosylceramidase / genetics*
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Homozygote
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Humans
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Levodopa / therapeutic use
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Male
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Middle Aged
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Mutation
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Parkinson Disease / drug therapy
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Parkinson Disease / etiology*
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Psychosine / analogs & derivatives
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Sphingosine / analogs & derivatives*
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Sphingosine / metabolism
Substances
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Psychosine
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Levodopa
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sphingosyl beta-glucoside
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endodeoxyribonuclease SspI
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Deoxyribonucleases, Type II Site-Specific
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GTYRAC-specific type II deoxyribonucleases
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Glucosylceramidase
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Sphingosine