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

Abstract

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.

Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1

“…A more recent report of 22 untreated children, including the 15 previously described, found a mean IQ of 67 (well below average) at a mean age of 2.28 years. 8 Across the population, the IQ decreased with increasing age, and all died in early childhood.…”

“…7,8 Past research has shown that HCT prevents progressive deterioration in cognitive outcomes into the extremely low average range among children with MPS IH, 9,10 although cognitive functioning remains below average for some children compared with same-aged peers. Regardless of statistical significance or comparisons with other groups, clinically meaningful cognitive improvement may be demonstrated with HCT treatment.…”

“…Shapiro and colleagues 8 reported cross-sectional assessments for 60 patients with MPS IH treated at five US and Canadian centers. Fourteen children assessed pre-HCT (≤ age 24 months), had a mean age of treatment of 7.5 months, and a mean pre-HCT IQ score of 91 (average range).…”

“…Shapiro and colleagues 8 analyzed cross-sectional data for 60 patients with MPS IH, of whom 14 were administered ERT prior to HCT and 46 were assessed post-HCT. Of those assessed post-HCT, 19 were assessed at ages 24–71 months and 27 after 71 months.…”

Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management

“…Clinical trials and follow-up studies of ERT in MPS I have demonstrated improvements in some somatic manifestations and functional outcomes in patients with attenuated MPS I. [8][9][10][11][12][13] Laronidase has also been found to be useful in the peritransplant period for patients with severe MPS I. 4,14 The use of ERT in the peritransplant period has been shown to be safe and has led to clinical improvements particularly in patients with significant cardiopulmonary disease before transplantation.…”