Abstract
The gangliosidoses are a group of lysosomal storage diseases characterized by the accumulation of these complex glycolipids in multiple organs of the body. They manifest a predominantly neurological phenotype, a fact that is probably related to their high prevalence in nervous tissues. The typical presentation is that of a progressive neurodegenerative disease with onset in early life followed by loss of acquired developmental milestones, dementia, and worsening neurological deficits. Early death is common, except perhaps in late-onset variants. Systemic manifestations in the form of visceromegaly or skeletal deformities are preferentially seen in the aggressive variants of GM1 gangliosidosis (i.e., infantile), whereas they are typically absent in GM2 gangliosidosis (except for Sandhoff’s disease, which may present with mild visceromegaly). Depending upon the severity of the enzymatic defect, they show different rates of clinical progression and involvement, with severe deficiencies leading to the most aggressive forms in an infantile and acute or subacute fashion, whereas milder ones have an onset later in life and slower clinical progression.