Clinical Course of GM₂ Gangliosidoses - A Correlative Attempt

Abstract

1. The clinical course of the early onset gangliosidoses can be explained on the basis of the developmental time course of different brain structures and functional systems.
In particular, the maturation of the four basic motor control systems - spinal cord, brain stem and cerebellum, basal gangIia, cerebral cortex - determines the appearance of certain motor deficits.
2. In late onset GM₂ gangliosidoses, however, regional preference of the storage process has to be assumed in order to explain certain characteristic features of the disorder.
3. An attempt is made to explain cellular dysfunction in GM₂ storage disorders on the basis of
a) developmental defects and/or destruction of the endoplasmatic reticulum and Golgi apparatus
b) distortion of the neuronal geometry.
4. Hyperirritability and epilepsy are possibly due to a dysequilibrium between excitatory and inhibitory postsynaptic influences caused by the distortion of the synaptic 'geometry on the nerve cell surface. Again, the clinical appearance of hyperirritability and the type of epilepsy are dependent upon the developmental age of the affected nervous system.

Key words

Gangliosidosis - Tay-Sachs disease - Sandhoff's disease - Blindness - Dementia - Epilepsy - Endoplasmatic reticulum - Dendritic spines