Details

Autor(en) / Beteiligte

• Muenzer, Joseph
• Burton, Barbara K
• Amartino, Hernan M
• Harmatz, Paul R
• Gutiérrez-Solana, Luis González
• Ruiz-Garcia, Matilde
• Wu, Yuna
• Merberg, David
• Alexanderian, David
• Jones, Simon A

Titel

Neurodevelopmental status and adaptive behavior of pediatric patients with mucopolysaccharidosis II: a longitudinal observational study

Ist Teil von

• Orphanet journal of rare diseases, 2023-11, Vol.18 (1), p.1-357, Article 357

Ort / Verlag

London: BioMed Central Ltd

Erscheinungsjahr

2023

Quelle

SpringerLink Journals - AutoHoldings

Beschreibungen/Notizen

• Mucopolysaccharidosis (MPS) II is a rare, X-linked lysosomal storage disease. Approximately two-thirds of patients have central nervous system involvement with some demonstrating progressive cognitive impairment (neuronopathic disease). The natural history of cognitive and adaptive function in patients with MPS II is not well-defined. This 2-year, prospective, observational study evaluated the neurodevelopmental trajectories of boys with MPS II aged [greater than or equal to] 2 years and < 18 years. Overall, 55 patients were enrolled. At baseline, mean (standard deviation [SD]) age was 5.60 (3.32) years; all patients were receiving intravenous idursulfase. Cognitive and adaptive function were assessed using the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) scores, respectively. Baseline mean (SD) DAS-II GCA and VABS-II ABC scores were 78.4 (19.11) and 83.7 (14.22), respectively, indicating low cognitive function and moderately low adaptive behavior. Over 24 months, modest deteriorations in mean (SD) scores were observed for DAS-II GCA (-3.8 [12.7]) and VABS-II ABC (-2.0 [8.07]). Changes in DAS-II GCA scores varied considerably, and data suggested the existence of four potential patient subgroups: (1) patients with marked early impairment and rapid subsequent decline, (2) patients with marked early impairment then stabilization, (3) patients with mild early impairment then stabilization, and (4) patients without impairment who remained stable. Subgroup analyses revealed numerically greater DAS-II GCA score reductions from baseline in patients aged < 7 years at baseline (vs. those aged [greater than or equal to] 7 years) and in patients with DAS-II GCA scores [less than or equal to] 70 at baseline (vs. those with scores > 70); between-group differences were nonsignificant. No clear subgroups or patterns were identified for individual changes in VABS-II ABC scores. In total, 49 patients (89.1%) reported [greater than or equal to] 1 adverse event (AE) and nine patients (16.4%) reported serious AEs. Some patients with MPS II had rapid declines in cognitive ability, whereas others remained relatively stable after an initial decline. These insights provide a basis for more detailed analyses of different patient subgroups, which may enhance the definition and understanding of factors that influence cognitive and adaptive function in MPS II.