TY - JOUR
T1 - Neurocognition across the spectrum of mucopolysaccharidosis type I
T2 - Age, severity, and treatment
AU - Shapiro, Elsa G.
AU - Nestrasil, Igor
AU - Rudser, Kyle
AU - Delaney, Kathleen
AU - Kovac, Victor
AU - Ahmed, Alia
AU - Yund, Brianna
AU - Orchard, Paul J.
AU - Eisengart, Julie
AU - Niklason, Gregory R.
AU - Raiman, Julian
AU - Mamak, Eva
AU - Cowan, Morton J.
AU - Bailey-Olson, Mara
AU - Harmatz, Paul
AU - Shankar, Suma P.
AU - Cagle, Stephanie
AU - Ali, Nadia
AU - Steiner, Robert D.
AU - Wozniak, Jeffrey
AU - Lim, Kelvin O.
AU - Whitley, Chester B.
N1 - Publisher Copyright:
© 2015 Elsevier Inc..
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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 MRI 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 HCT were associated with cognitive ability. In attenuated MPS I, 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 MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association 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.
AB - 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 MRI 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 HCT were associated with cognitive ability. In attenuated MPS I, 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 MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association 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.
KW - Genotypes
KW - Mucopolysaccharidosis Type I
KW - Neurocognition
KW - Neuroimaging
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U2 - 10.1016/j.ymgme.2015.06.002
DO - 10.1016/j.ymgme.2015.06.002
M3 - Article
C2 - 26095521
AN - SCOPUS:84940893067
SN - 1096-7192
VL - 116
SP - 61
EP - 68
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -