The Burden of Airway Disease in Mucopolysaccharidoses: Evidence Across Subtypes.

Abstract

To synthesize the prevalence and subtype-specific patterns of airway manifestations in mucopolysaccharidoses (MPS) and summarize related morbidity and mortality. PubMed, CINAHL, Ovid Embase, Ovid MEDLINE, and Ovid All EBM Reviews. PRISMA-ScR guided scoping review of English and French-language studies reporting airway manifestations in ≥ 5 patients up to June 2026. Pooled prevalences with 95% confidence intervals (CI) were estimated using proportional meta-analysis. Of 2359 records, 65 case series (3715 participants; Level 4 evidence) were included. Upper-airway soft tissue hypertrophy was common: adenoid hypertrophy ranged from 52.5% (MPS IV; 95% CI, 21.0-82.1) to 78.5% (MPS I; 95% CI, 23.9-97.7); tonsillar hypertrophy ranged from 38.5% (MPS I; 95% CI, 17.5-64.9) to 59.5% (MPS II; 95% CI, 34.6-80.4). Macroglossia was frequent, with the highest prevalence in MPS II (79.7%; 95% CI, 16.5-98.7). Laryngotracheal involvement varied, with tracheal narrowing reaching 92.3% (95% CI, 7.0-99.9) in MPS II and 85.4% (95% CI, 38.3-98.2) in MPS IV. Obstructive sleep apnea was highly prevalent across subtypes (MPS I, 61.7%; 95% CI, 45.3-75.9; MPS II, 75.3%; 95% CI, 43.1-92.4; MPS VI, 83.7%; 95% CI, 48.0-96.6). Tracheotomy was required in 7.0% (95% CI, 4.9-9.9), and respiratory-related deaths occurred in 10.4% (95% CI, 5.2-19.9) of patients with available data. Airway disease in MPS is common, multilevel, and clinically consequential, with substantial burdens of OSA and progressive laryngotracheal pathology. Early, systematic, longitudinal airway assessment is essential to guide counseling and management across MPS subtypes.