Objective: To describe a case with a new genetic variant of type 3 Gaucher disease presenting with stimulus-sensitive and action myoclonus in the presence of selective dentate abnormalities.
Design: Clinical, pathologic, and molecular genetic studies.
Setting: Medical school departments.
Patient: A 6-year-old girl with type 3 Gaucher disease experienced progressively crippling generalized stimulus-sensitive and action myoclonus. Repeated electroencephalographic examination did not show cortical activity associated with the myoclonus, suggesting its subcortical origin. Neuropathological examination revealed selective degeneration of the cerebellar dentate nucleus and dentatorubrothalamic pathway in the face of essentially complete lack of storage in the brain. Mutation analysis identified the following 2 mutant alleles: one with a V394L mutation and the other with the lesion RecTL (D409H + L444P + A456P + V460V), which resulted from a recombination event, with the pseudogene located 16 kilobases downstream from the structural gene.
Conclusion: Given the restricted abnormalities, this genetically unique case provides insight into the pathogenesis of myoclonus and suggests a prominent role for the cerebellar dentate nucleus in its genesis.