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.
Subjects must have a documented gangliosidosis disease.
Subjects must be able to complete appropriate neuropsychological and neurobehavioral assessments.
Late-onset gangliosidosis subjects must be able to tolerate a head MRI.
None
Any infant or juvenile with Tay-Sachs disease, Sandhoff disease, or GM1 gangliosidosis; and any adult with a late-onset gangliosidosis disease
Cohort
Prospective
Not listed
Change in Child Developmental Status as Assessed by Neuropsychological Tests
Neuropsychological testing data will be collected at baseline and annually, that measure fine and gross motor skills, visual tracking and attention, verbal and non-verbal communication, and emotional and social behaviors. For infantile and juvenile Tay-Sachs disease, Sandhoff disease and GM1 gangliosidosis-affected subjects, age- and ability-appropriate neurobehavioral and neurodevelopmental testing will include instruments such as the Bayley Scales of Infant Development (Third Edition), and the Vineland Adaptive Behavior Scales.
Ascertainment of Enzyme Activity Levels
If either of the following diagnostic measures have been performed in the course of subjects' clinical care not connected with this study, the resulting data will be collected: for Tay-Sachs and Sandhoff disease-affected patients, levels of hexosaminidase enzyme activity; or for GM1 gangliosidosis-affected patients, levels of β-galactosidase enzyme activity. Determinations of these enzyme activity levels are a requisite part of the diagnostic process in all of the gangliosidosis diseases.
Medication Regime
If any medications are given to subjects during the course of subjects' clinical care not connected with this study, the medications will be identified, quantified and recorded.
Clinical Assessments
Clinical assessments will be performed that measure initial symptomology, along with the appearance and evolution of symptoms over time. For infants and juveniles, these may include: evaluation of motor control, gain and/or loss of developmental milestones, hyperacusis, seizures, macrocephaly, the appearance of retinal "cherry-red spots" ascertained by ocular exam, personal interaction, and reflexes. For adults, assessments may include: coordination, psychological disorder, verbal skills, muscle wasting with weakness, fasciculations, and posture abnormalities.
Changes in Child Brain Structure Development and Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination
For infantile and juvenile Tay-Sachs disease, Sandhoff disease and GM1 gangliosidosis-affected subjects, if any MRI brain imaging is performed during the course of subjects' clinical care not connected with this study, these MRI brain imaging data will be captured for this study. Any developmental abnormality, and the volumes of specific brain structures imaged, will be measured and the resulting data recorded. If data from multiple MRI examinations performed at different times in any given patient's life become available, the resulting brain structure measurements will be compared across time, and analyzed in order to reveal progressive changes in brain structure, if any have occurred.
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University of Minnesota
Lead sponsor
Rare Diseases Clinical Research Network
Collaborator
National Center for Advancing Translational Sciences (NCATS)
Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Lysosomal Disease Network
Collaborator
