Toward a Core Outcome Set for Head, Neck, and Respiratory Disease in Mucopolysaccharidosis Type II: Systematic Literature Review and Assessment of Heterogeneity in Outcome Reporting

Abstract The mucopolysaccharidoses (MPS) are a relatively uncommon group of inherited metabolic disorders, with significant negative implications for life span and aspects of quality of life. Their rarity means that producing evidence to guide best practice has often entailed assimilating findings from multiple studies. Core outcome sets (COS) are being increasingly used across medicine as a potential solution to the problems arising from heterogeneous reporting of outcomes in effectiveness studies. A COS is a recommended minimum set of outcomes that should be measured for a given condition in an effectiveness study, with the ultimate aim of increasing the value of clinical information by enabling meaningful comparison and combination of data from various sources. A systematic review identified 41 outcomes measured in published studies and ongoing and completed clinical trials, with individual outcomes being measured using a variety of measurement instruments/tools. This work represents the important initial steps in the development of COS for head, neck, and respiratory disorders in MPS type II, raising awareness of the extent of heterogeneity in outcome reporting and determining the scope of outcomes and corresponding instruments currently used. The next step will be to use the generated "longlist" of outcomes to develop an electronic Delphi prioritization exercise with the intention of reaching a consensus regarding the most important outcomes to measure in effectiveness studies for head, neck, and respiratory disease in MPS type II.

Obstructive Sleep Apnea in MPS: A Systematic Review of Pretreatment and Posttreatment Prevalence and Severity

Abstract The mucopolysaccharidoses (MPSs) are a group of inherited, metabolic disorders characterized by progressive multisystem accumulation of partially degraded glycosaminoglycans. This manifests with multilevel airway obstruction, presenting with obstructive sleep apnea (OSA). We systematically reviewed the literature to determine the severity and prevalence of OSA in MPS based on polysomnography analysis. Fifteen studies with 294 participants met the inclusion criteria for review. The pretreatment prevalence of OSA in MPS was 81% with a mean apnea-hypopnea index (AHI) of 10.4. Patients with MPS I are most significantly affected, with 75% suffering with moderate to severe OSA (mean AHI, 16.6). Enzyme replacement therapy (ERT) results in an almost significant reduction in OSA in MPS I (P = .06), while adenotonsillar surgery significantly improves AHI (P = .002). Obstructive sleep apnea least affects MPS III. There is a lack of long-term post-ERT and hematopoietic stem cell transplant data relating to OSA outcomes in this population, with further prospective studies required to determine the ongoing response to treatment.