An exploratory study of brain function and structure in mucopolysaccharidosis type I: long term observations following hematopoietic cell transplantation (HCT).

ABSTRACT

AIM: Although hematopoietic cell transplantation (HCT) arrests the cognitive decline in mucopolysaccharidosis type IH (Hurler syndrome, MPS IH), these children continue to have neuropsychological deficits as they age. Both compromised attention and effects on white matter have been observed in cancer patients who have had chemotherapy. Therefore, we explored the effects of disease and treatment on brain function in children with MPS I who have had HCT with those with attenuated MPS I treated with enzyme replacement therapy (ERT). SUBJECTS: 7 MPS IH participants at least 5 years post-HCT were compared with 7 attenuated participants who were treated with ERT. MEASURES: IQ, attention, spatial ability, and memory were assessed. Medical history and an unsedated MRI scan using diffusion tensor imaging (DTI) were acquired. RESULTS: Despite clinically equivalent IQ and memory, children with MPS IH had poorer attention span than those with attenuated MPS I as well as decreased fractional anisotropy (FA) of the corpus callosum. A relationship between attention scores and FA was found in the MPS IH group but not the attenuated group. FA was also related to the frequency of medical events. INTERPRETATION: In children with MPS IH, both the treatment and the disease affect attention functions associated with poor white matter integrity.