MPS Disease Longitudinal Study of Treatment and Outcomes Across the Lifespan

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The mucopolysaccharidoses are monogenic, heritable disorders of lysosomal malfunction that cause progressive multi-system organ damage. Early on, it was thought that the physical manifestations of MPS commenced in childhood, but we now know that glycosaminoglycan deposition begins in utero and that treatment beginning early in life, even infancy, does not ameliorate the burden of disease. Importantly, while the primary effects of disease vary by genetic subtype—for example MPS I, II, and III come with a significant cognitive impact, while MPS IV and VI, have central nervous system involvement that does not include cognition—all of the MPS disorders, regardless of central nervous system burden, comprise significant skeletal and organ deficits that results in lifelong disability; and that this disability exists regardless of treatment. Current therapies have shown some effect in ameliorating the devastating brain disease, but have had little somatic effect—especially as it relates to skeletal (bone) and cardiac (valve) involvement. As treatment options for the MPS conditions continue to grow, and expand to include gene therapy, a systematic, thorough categorization of disease effect across the lifetime individuals with MPS is more relevant than ever. Adding to the need for early, longitudinal, descriptive data is the advent of newborn screening for MPS I to the panels in several states. Those identified via a newborn screening present a unique opportunity to collect data from individuals with MPS I beginning at birth. This data, in conjunction with that collected by our research team over the last 10 years, provides the richest, most complete dataset available against which to measure new therapy. Adding to the dataset in the ways described here, will lead to specific recommendations on how to proceed therapeutically, after a diagnosis (via newborn screening or otherwise) for any MPS condition. The Lysosomal Disease Network structure allows us to incorporate data from Centers of Excellence geographically dispersed across the US and Canada to collect cross-tabulated data from the widest possible patient population that: 1. Quantifies abnormalities and rates of progression in neurodevelopment by disease subtype, 2. Characterizes social, emotional, and behavioral profiles; correlated with treatment by disease subtype, 3. Determines abnormalities in brain morphometry and white matter microstructure to define developmental pathways by disease subtype, 4. Quantifies the burden of physical disability across organ systems and how those disabilities impact development and psychosocial function, 5. Assess the full impact of MPS on skeletal and cardiac systems across treatment modalities, and 6. Identify the incidence pattern of disease expression of infants with Hurler syndrome identified by newborn screening, and how current stem cell transplant leads to disease-related morbidity and mortality. Every aim presented will be evaluated in context with each other to provide detailed, multi-dimensional data designed to define systematic burden as a measure for future therapy.