Longitudinal Studies of Brain Structure and Function in MPS Disorders

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.

Inclusion Criteria:

- Any MPS I, II, IV, VI or VII child or adult aged 6 years of age or older

Exclusion Criteria:

- Exclusion Criteria for Neuroimaging:

- Participants with:

- Pacemakers

- Any indwelling electronic device including programmable shunts

- Orthodontic braces unless they are not made of metal

- Other implanted metal in the body other than titanium

- Unable to stay still during MRI because of low cognitive function,
behavioral dysregulation, or young age, if the patient is not a clinical
patient having sedation/anesthesia

- Pregnancy

- Exclusion Criteria for Neuropsychological and Neurobehavioral Testing

- Participants who:

- Are too functionally impaired for testing