Mucopolysaccharidosis Type I, Mucopolysaccharidosis Type II, Mucopolysaccharidosis Type IV, Mucopolysaccharidosis Type VI, Mucopolysaccharidosis Type VII
Conditions
Keywords
Mucopolysaccharidosis, Longitudinal, Brain, Cognition, Quality-of-Life, Hurler syndrome, Hunter syndrome, Hurler-Scheie syndrome, Scheie syndrome, Maroteaux-Lamy syndrome, MPS I, MPS II, MPS VI, Mucopolysaccharidosis type I, Mucopolysaccharidosis type II, Mucopolysaccharidosis type VI, MPS IV, MPS VII, Mucopolysaccharidosis type IV, Mucopolysaccharidosis type VII, Morquio syndrome, Sly syndrome
Brief summary
Neurobehavioral function and quality of life are compromised in many patients with mucopolysaccharidosis (MPS) disorders. The long-term goals of this research are to: 1) more accurately inform patients/parents regarding potential neurobehavioral outcomes; 2) develop sensitive measures of disease progression and central nervous system (CNS) treatment outcome; and 3) help clinical researchers develop direct treatments for specific brain structures/functions. The investigators hypothesize that specific and localized neuroimaging and neuropsychological findings and their relationship will be distinct for each MPS disorder. It is further hypothesized that without treatment, functions will decline and structure will change over time in a predictable fashion, and will be related to locus of abnormality and stage of disease.
Detailed description
The mucopolysaccharidoses (MPS diseases) are lysosomal disorders (inborn errors of metabolism) that progressively affect most organ systems in the body, usually beginning in childhood. Recent treatment advances have produced amelioration of some of these malfunctions, but notably brain and bone have been difficult to effectively treat. This research addresses the brain abnormalities in the MPS disorders, about which little is known. The objectives of this research are: 1. to identify abnormalities of central nervous system (CNS) structure and function as well as to measure quality-of-life (QOL) in both treated and untreated MPS patients over time. The investigators will accomplish this through longitudinal studies of enrolled patients in designated centers in North America. 2. to develop quantitative measurements of change, including direct measurement of neuropsychological function; surrogate MRI markers; and biomarkers to measure stage of disease and treatment outcomes. 3. to examine the degree to which independent variables have an impact on both functional and structural outcome. Independent variables may include, but are not limited to: age at first treatment, severity of disease, types of medical abnormalities, nature of genetic mutation, medical events, and sensory abnormalities. 4. to examine how treatments such as Enzyme Replacement Therapy (ERT), Hematopoietic Cell Transplant (HCT), substrate reduction, and other palliative and rehabilitative therapies differentially affect CNS structure and function, as well as the subject's quality of life.
Interventions
None listed
Sponsors
Rare Diseases Clinical Research Network
National Center for Advancing Translational Sciences (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Lysosomal Disease Network
University of Minnesota
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Any MPS I, II, IV, VI or VII child or adult aged 6 years of age or older
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognitive Ability (IQ) | Baseline, Year 1, Year 2, Year 3 | Age-appropriate IQ tests will be administered at baseline and during subject's annual visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life | Baseline, Year 1, Year 2, Year 3 | Age-appropriate Quality of Life measures will be administered at baseline and during subject's annual visit. |
| Change in Neuropsychological Status | Baseline, Year 1, Year 2, Year 3 | Memory, Attention, Visual Spatial, and Visual Motor functions will be assessed with age-appropriate measures administered at baseline and during subject's annual visit. |
| Change in Emotional and Behavioral Health | Baseline, Year 1, Year 2, Year 3 | Age-appropriate measures of emotional and behavioral health will be administered at baseline and during subject's annual visit. |
| Change Shown in Magnetic Resonance Imaging of the Brain | Baseline, Year 1, Year 2, Year 3 | Magnetic resonance imaging of each subject's brain will be performed at baseline and during subject's annual visit to acquire volumetric, diffusion tensor imaging (DTI), and resting state data. These data will be analyzed to identify any changes occurring over time. |
| Change in Adaptive Functions | Baseline, Year 1, Year 2, Year 3 | Vineland Adaptive Behavior Scales, a measure of communication, daily living skills, socialization and motor function, will be administered at baseline and during subject's annual visit. |
Countries
Canada, United States
Outcome results
None listed