Seizures are a major manifestation of several lysosomal storage diseases. This chapter discusses neurons of lipids or glycoconjugates, which include the neuronal ceroid lipofuscinoses, the gangliosidoses, the sialidoses, and two of the mucopolysaccharidoses, Hunter syndrome and Sanfilippo disease. The galactolipidoses, Krabbe disease, and metachromatic leukodystrophy (MLD), are also discussed, because they secondarily affect neurons and clinically present with seizures. Finally, two transport disorders, one lysosomal, Niemann-Pick disease type C, and the other, Menkes disease, a non-lysosomal X-linked disorder, join these other seizure-provoking hereditary metabolic syndromes because of identifiable metabolic abnormalities within neurons. Progressive neuropsychiatric deterioration appears from the late infantile period manifesting as ataxia, dystonia, dysphagia, dysarthria, seizures, cataplexy, and cognitive deterioration. Seizures are almost constant and include asymmetric myoclonic jerks that can be stiumulus-provoked. Plasma dopamine and dihydroxyphenylacetic acid are elevated due to low dopamine beta-hydroxylase activity.

This chapter presents the pathophysiology, prognosis, diagnostic tests for sialidosis and Gaucher disease (GD). The epileptic phenotype resulting from sialidoses and from the subtypes of GD presents with myoclonus and generalized seizures and belongs to the category of progressive myoclonus epilepsies (PMEs). Sialidoses are classified in two types presenting with different phenotypes. In both types of sialidosis, electrophysiological studies performed at onset of seizure or myoclonus show paroxysmal electroencephalographic (EEG) activity, which can either present as polyspike-waves or as fast activities. The positive diagnosis can be based on the determination of very low blood glucocerebrosidase enzyme activity. A proposed treatment is substrate reduction therapy (SRT), which is based on chronic oral administration of an inhibitor of the biosynthesis of glucosylceramide and higher glycosphingolipids (miglustat), This inhibitor can cross the blood-brain barrier and might help reducing central nervous system complications in some GD patients.