a natural history study of the gangliosidoses

Conditions: Tay-Sachs Disease; Sandhoff Disease; Late Onset Tay-Sachs Disease; GM1 Gangliosidosis; GM2 Gangliosidosis

Summary: hypothesis: to characterize and describe disease progression and heterogeneity of the gangliosidosis diseases. this research study seeks to develop a quantitative method to delineate disease progression for the gangliosidosis diseases (tay-sachs disease, sandhoff disease, and gm1 gangliosidosis) in order to better understand the natural history and heterogeneity of these diseases. such a quantitative method will also be essential for evaluating any treatments that may become available in the future, such as gene therapy. the data from this study will be necessary to provide end-points for future therapies, guide medical decisions about treatment, provide objective measurement of treatment outcomes, and accurately inform parents regarding potential outcomes.

the infantile form of gm2 and gm1 gangliosidosis diseases ("classic" infantile) is the most common. infants with tay-sachs disease, sandhoff disease or gm1 gangliosidosis appear normal at birth, but at approximately 6-10 months of age begin to manifest progressive weakness and loss of muscle strength, such as loss of the ability to sit up or turn over. they may evidence deafness, and display decreased attentiveness. this is followed by rapid deterioration of motor skills and slowed mental development (neurodegeneration), often with seizures. retinal involvement leads to visual impairment and eventual blindness. death typically occurs by the age of five. currently there is no treatment for tay-sachs disease, sandhoff disease or gm1 gangliosidosis. late onset tay-sachs disease ("lots") occurs in patients beginning in their twenties or thirties, and is characterized by poor motor coordination and psychotic behaviors. patients with lots also have decreased life expectancy, although to a lesser degree than those with infantile or juvenile tay-sachs or sandhoff diseases. currently there is no treatment for lots. this study is comprised of two different 'arms.' the first arm, entitled aim 1, will focus on the developmental course of infantile and juvenile tay-sachs disease, sandhoff disease, and gm1 gangliosidosis. longitudinal data from individuals with these diseases will be collected in order to delineate the natural history of these diseases. this data will help to objectify disease progression, and can be used to create a disease stage and severity index. the second arm, entitled aim 2, will focus on lots and will seek to understand the progression of central nervous system disease, with special focus upon cerebellar and frontal systems. this will be accomplished by using quantitative methods including neuroimaging and neuropsychological measures that explore motor and executive functions, visual-spatial and emotional-behavioral dysfunction.

Eligibility criteria:
inclusion criteria: 1. subjects must have a documented gangliosidosis disease. 2. subjects must be able to complete appropriate neuropsychological and neurobehavioral assessments. 3. late-onset gangliosidosis subjects must be able to tolerate a head mri. exclusion criteria: 1. there are no exclusion criteria, beyond a desire not to participate.

Keywords: tay-sachs disease sandhoff disease late onset tay-sachs disease lots hexosaminidase a deficiency hexosaminidase a and b deficiency infantile tay-sachs disease adult-onset tay-sachs disease prospective natural history gm1 gangliosidosis gangliosidoses β-galactosidase β-galactosidase deficiency hexosaminidase hexosaminidase deficiency tay-sachs sandhoff juvenile tay-sachs juvenile tay-sachs disease late onset tay-sachs juvenile sandhoff juvenile sandhoff disease gm2 gangliosidosis