OBJECTIVES: Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare lysosomal storage disorder that leads to severe functional declines in childhood and adolescence. Because no disease-specific instruments currently exist for MPS II, this study sought to confirm the previously established psychometric properties of the CHAQ in this disease population. METHODS: All twelve families participating in a Phase I/II enzyme replacement therapy trial for MPS II agreed to participate in the IRB-approved CHAQ confirmatory validation study. Assessments were completed during regular twice-monthly study visits. Only patients 12 years and older completed the instrument although all parents were asked to complete the questionnaire as a proxy responder. Face validity, internal reliability, domain intercorrelation coefficients, parent-child correlations, and test-retest reliability were assessed on the overall CHAQ disability index. RESULTS: Nine patients (mean age 18.0 ± 4.3 years) and one parent per child completed the CHAQ; three additional patients (mean age 9.7 ± 1.5 years) had parent-reported assessments only due to age limitations. The instrument showed good internal reliability (Cronbach's alpha = 0.86 [parents] and 0.83 [patients]) and good reproducibility in a test-retest over a three-week period (Spearman correlation coefficient = 0.81, p = 0.0014 [parent]; 0.94, p = 0.0002 [patient]). Parent-child correlation was moderately weak at 0.38 (p = 0.317), a divergence commonly seen in child/adolescent outcome measurements. Intercorrelation coefficients of each domain with the overall disability index were in the moderate range (mean rs = 0.6 for parents, rs = 0.5 for patient). Although face validity was acceptable, the CHAQ still did not completely address certain functional challenges specific to MPS II. CONCLUSION: The psychometric properties of the CHAQ appear acceptable in measuring general disability and functional status in MPS II. Further assessment of its sensitivity and discriminant validity are needed as part of ongoing clinical trials. Development of a disease-specific instrument appears warranted given the unique functional challenges of patients with MPS II.