Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment

作者：Shapiro Elsa G^*; Nestrasil Igor; Rudser Kyle; Delaney Kathleen; Kovac Victor; Ahmed Alia; Yund Brianna; Orchard Paul J; Eisengart Julie; Niklason Gregory R; Raiman Julian; Mamak Eva; Cowan Morton J; Bailey Olson Mara; Harmatz Paul; Shankar Suma P; Cagle Stephanie; Ali Nadia; Steiner Robert D; Wozniak Jeffrey; Lim Kelvin O; Whitley Chester B

来源：Molecular Genetics and Metabolism, 2015, 116(1-2): 61-68.

DOI：10.1016/j.ymgme.2015.06.002

• Mucopolysaccharidosis Type I
• Neurocognition
• Genotypes
• Neuroimaging

Objectives: Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden.
Methods: Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MR1 and compared to 96 normal controls.
Results: Prior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HO' were associated with cognitive ability. In attenuated MPS 1,40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH.
Conclusions: Cognitive impairment, a major difficulty for many MPS1 patients, is associated with genotype, age at treatment and somatic disease burden. IQassociation with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management.

• 出版日期2015-10