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Background Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by cognitive impairment in most patients. This post hoc analysis evaluated changes in cognitive function, adaptive behavior and functional outcomes in patients with neuronopathic MPS II over time. Fifty-five children with MPS II were enrolled in a 24-month observational study (NCT01822184). The Differential Ability Scales, second edition (DAS-II; early years battery for ages 2 years 6 months to 6 years 11 months, school age battery for ages 7 years to 17 years 11 months), Vineland Adaptive Behavior Scales, second edition (VABS-II) and the Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) were performed at baseline and 3-month intervals over 2 years. A subgroup of 38 children with a DAS-II General Conceptual Ability (GCA) score of 55–85 (below average–very low abilities) at any time during the study were included in this analysis. Results Mean (standard deviation [SD]) early years DAS-II GCA score decreased from 73.4 (15.7, n = 22) at baseline to 62.7 (34.9, n = 6) at month 24. For the six patients with early years GCA assessments at baseline and month 24, mean (SD) GCA scores decreased from 72.3 (21.3) at baseline to 62.7 (34.9) at month 24. School age GCA scores were stable over 2 years: mean (SD) 72.4 (11.8, n = 10) at baseline; 74.3 (12.3, n = 8) at month 24. Mean (SD) VABS-II Adaptive Behavior Composite (ABC) scores were stable throughout the study (baseline, 81.8 [11.8, n = 36]; month 24, 81.0 [10.2, n = 13]). Some associations between items and domains of HS-FOCUS (p Conclusions The DAS-II measured changes in cognitive function over 2 years in younger patients with MPS II, whereas cognitive function in older patients remained stable. Further research is required to confirm the content validity of the DAS-II in different patient populations with MPS II. The VABS-II and HS-FOCUS were not sensitive tools for measuring behavioral and functional changes over 2 years. These findings may inform selection of appropriate cognitive and behavioral assessment tools for future studies.

Hunter syndrome, or mucopolysaccharidosis (MPS) II, is a rare lysosomal disorder characterized by progressive, multi-system disease. As most symptoms cannot be reversed once established, early detection and treatment prior to the onset of clinical symptoms are critical. However, it is difficult to identify affected individuals early in disease, and therefore the long-term outcomes of initiating treatment during this optimal time period are incompletely described. We report long-term clinical outcomes of treatment when initiated prior to obvious clinical signs by comparing the courses of two siblings with neuronopathic Hunter syndrome (c.1504T>G[p.W502G]), one who was diagnosed due to clinical disease (Sibling-O, age 3.7 years) and the other who was diagnosed before disease was evident (Sibling-Y, age 12 months), due to his older sibling’s findings. The brothers began enzyme replacement therapy within a month of diagnosis. Around the age of 5 years, Sibling-O had a cognitive measurement score in the impaired range of

OBJECTIVE: The WHODAS-II was substantially modified for use in the World Mental Health Surveys. This article considers psychometric properties and implications of filter items used to reduce respondent burden of the modified WHODAS-II. STUDY DESIGN AND SETTING: Seventeen surveys in 16 countries administered a modified WHODAS-II to population samples (N=38,934 adults). Modifications included introducing filter questions for four subscales and substituting questions on the number of days activity was limited for the Life Activities domain. We evaluated distributional properties, reliability, and validity of the modified WHODAS-II. RESULTS: Most respondents (77%-99%) had zero scores on filtered subscales. Lower bound estimates of internal consistency (alpha) for the filtered subscales were typically in the 0.70s, but were higher for the Global scale. Loadings of subscale scores on a Global Disability factor were moderate to high. Correlations with the Sheehan Disability Scale were modest but consistently positive, while correlations with SF-12 Physical Component Summary were considerably higher. Cross-national variability in disability scores was observed, but was not readily explainable. CONCLUSIONS: Internal consistency and validity of the modified WHODAS-II was generally supported, but use of filter questions impaired measurement properties. Group differences in modified WHODAS-II disability scores may be compared within, but not necessarily across, countries. These activities were supported by the United States National Institute of Mental Health (R01MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R01-TW006481). The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H). The ESEMeD project was funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123), the Piedmont Region (Italy), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain. The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575). The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the Robert Wood Johnson Foundation (RWJF; Grant 044708)