6703: Lysosomal Disease Network Longitudinal Study of the Mucopolysaccharidoses

Background

Mucopolysaccharidosis (MPS) types I, II, III, IV, VI and VII, are inherited diseases that result from the bodies inability to break down large sugar molecules that are by-products of metabolism. MPS affects most organs of the body and causes abnormalities in the liver, spleen, bones, and brain. We are studying the central nervous system (primarily the brain) and bones so we can better understand the nature of the problems individuals with MPS I, II, III, IV, VI and VII have so we can find ways of better treating these problems. We would like to find out about the changes in the brain of individuals with MPS I, II, IV, VI and VII using data from MRI and neuropsychological tests. We would like to collect tissue samples to see why bones and joints don’t seem to respond to treatment very well. We would like to find newborns with MPS from newborn screening, to see how treating MPS very early in life changes outcomes. We want to see how heart function changes over time in response to different treatments. This is a longitudinal study that collects data from medical records and by interviewing people with MPS and their parent and/or caregiver. We will collect medical information on your diagnosis, treatments (if any), neuropsychology and behavior, surgical record, cardiology record, and transplant outcome (if any).

The research objectives are:

Data from the following areas will be collected and assessed during this study; measured outcomes will be evaluated in concert with each other:

1. Neurocognitive development: To characterize all MPS types with particular focus on the very young, including those identified via newborn screening, as well as the aging MPS populations in order to understand the varying manifestations of disease.
2. Psychosocial Model: to gather data from questionnaires that can help characterize the behavioral, emotional, and social profiles, along with profile trajectories, across age spectrums for MPS disorders while assessing how earlier treatment influences psychosocial outcomes for MPS-affected individuals and their families.
3. Neuroimaging: To establish sensitive MRI markers that will be utilized in future clinical trials for MPS.
4. Physical Symptom Score (PSS) and Infant Physical Symptom Score (IPSS): To utilize a quantified method, such as the PSS and IPSS questionnaires of general health, to assess outcomes and changes in somatic disease in individuals with MPS disorders while examining the association with neurocognition, neuroimaging, psychosocial functioning, and quality of life outcomes.
5. Skeletal System: To identify defects in enzyme uptake, secretion and trafficking within the bone and tissue cells that regulate bone development and inflammation.
6. Cardiopulmonary: To aid the clinician, who often treats adults with MPS suffering both cardiac and respiratory dysfunction, as there is little guidance available to evaluate the significance of each process in the overall presentation of the individual.
7. Hematopoietic cell transplant: To better understand the benefits that newborn screening for Hurler syndrome will provide in regard to outcomes following hematopoietic stem cell transplant (HSCT).

About this Study

This is a longitudinal study of up to 100 individuals with either MPS I, II, III, IV, VI and VII. You will be asked to:

• Share data on your clinical care program
• Share data on brain MRIs that are a part of your clinical care program
• Share data on your medical background
• Share information on your disease causing mutation
• Share any “left over” bone and tissue that would otherwise be discarded when you have an orthopedic surgery.

Enrollment Criteria

Inclusion Criteria:

• Participant diagnosed with any MPS disorder, including those who:
  • Have Hurler syndrome and have undergone transplant
  • Have any MPS and are on any therapy including ERT
  • Are not currently using any therapy
• Pregnant individuals can participate, but will not undergo MRI
• Willing to provide extra tissues collected during a clinically ordered surgical procedure (relevant to those undergoing surgery only)

Exclusion Criteria:

• Unwilling to provide consent
• Any individual the PI feels is not suited for the study
• Individuals whose participation would increase their health risk,
• Non-English speakers without witness
• Cognitively impaired adults unable to consent who do not have a legal guardian
• Prisoners