Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Longitudinal Studies of Brain Structure and Function in MPS Disorders

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.

Eligibility: 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

Relevance to patient case: not relevant