Retrospective Natural History Study of neurodevelopment in neuronopathic Mucopolysaccharidosis Type II
Main Article Content
Abstract
Mucopolysaccharidosis Type II (MPS II) is a X-linked lysosomal storage disease caused by deficiency of iduronate-2-sulfatase (I2S) leading to accumulation of glycosaminoglycans and in the neuronopathic form, results in irreversible neurocognitive decline. The objectives of this study were to better understand the developmental trajectories of patients with neuronopathic MPS II across multiple domains and to identify timepoints where patients deviate outside of typical development and where skill acquisition plateaus.
This study presents a retrospective non-interventional medical records review of the neurodevelopmental natural history of patients with neuronopathic MPS II using the Mullen Scales of Early Learning (MSEL) Visual Reception, Expressive Language, Receptive Language, and Fine Motor scales. Function was characterized relative to MSEL normative ±1SD and ±2SD boundaries.
MSEL natural history data was available for 32 patients. The majority of the children were on enzyme replacement therapy. Developmental trajectories deviated below –1SD from the normative mean at a mean chronological age range from 12.8 (Expressive Language) to 19.5 months (Visual Reception) and below -2SD from 24.0 (Fine Motor) to 29.3 months (Visual Reception). The mean chronological age where skill acquisition plateaued ranged from 66.1 to 74.6 months while the developmental age equivalence score where skill acquisition plateaued ranged from 25.7 to 29.9 months. Slowing in the rate of skill acquisition was present very early in development and varied by baseline function and chronological age. Visual Reception skill acquisition when developmental function was -1SD from the normative mean was 5.8 months/year, at -2SD was 4.7 months/year and, from -2SD to peak skill acquisition, the mean rate was 1.6 months/year.
Results of this study support that developmental delay in patients with neuronopathic MPS II occurs across multiple domains very early in development and that the rate of skill acquisition varies by baseline function and chronological age. Although some children may acquire a small number of skills until they are 5–6 years old, function does not typically exceed the 2–3-year-old level and the rate of change per year is thereafter very small. Use of a multi-domain measure is important to understand disease impacts and developmental variability in neuronopathic MPS II.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Wraith JE, Scarpa M, Beck M, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008/03/01 2008;167(3):267-277. doi:10.1007/s00431-007-0635-4
3. Young ID, Harper PS, Newcombe RG, Archer IM. A clinical and genetic study of Hunter's syndrome. 2. Differences between the mild and severe forms. J Med Genet. Dec 1982;19(6):408-11. doi:10.1136/jmg.19.6.408
4. Holt J, Poe M, Escolar M. Natural progression of neurological disease in mucopolysaccharidosis type II. Pediatrics. 05/01 2011;127:e1258-65. doi:10.1542/peds.2010-1274
5. Shapiro EG, Jones SA, Escolar ML. Developmental and behavioral aspects of mucopolysaccharidoses with brain manifestations - neurological signs and symptoms. Mol Genet Metab. Dec 2017;122S:1-7. doi:10.1016/j.ymgme.2017.08.009
6. Holt J, Poe MD, Escolar ML. Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II. J Pediatr. 2011/08/01/ 2011;159(2):320-326.e2. doi:https://doi.org/10.1016/j.jpeds.2011.03.019
7. Link B, de Camargo Pinto LL, Giugliani R, et al. Orthopedic manifestations in patients with mucopolysaccharidosis type II (Hunter syndrome) enrolled in the Hunter Outcome Survey. Orthop Rev (Pavia). Sep 23 2010;2(2):e16. doi:10.4081/or.2010.e16
8. Shapiro EG, Eisengart JB. The natural history of neurocognition in MPS disorders: a review. Mol Genet Metab. May 2021;133(1):8-34. doi:10.1016/j.ymgme.2021.03.002
9. Phillips D, Cho Y, Mulatya C, Nevoret M-L, Poe M, Escolar M. Natural history of neurodevelopment in neuronopathic mucopolysaccharidosis type II (MPS II): Mullen Scales of Early Learning (MSEL) cognitive, motor and language developmental trajectories. Mol Genet Metab. 02/01 2022;135:S97. doi:10.1016/j.ymgme.2021.11.253
10. Barone R, Pellico A, Pittala A, Gasperini S. Neurobehavioral phenotypes of neuronopathic mucopolysaccharidoses. Ital J Pediatr. Nov 16 2018;44(Suppl 2):121. doi:10.1186/s13052-018-0561-2
11. Jones SA, Almássy Z, Beck M, et al. Mortality and cause of death in mucopolysaccharidosis type II - a historical review based on data from the Hunter Outcome Survey (HOS). J Inherit Metab Dis. Aug 2009;32(4):534-43. doi:10.1007/s10545-009-1119-7
12. Parini R, Rigoldi M, Tedesco L, et al. Enzymatic replacement therapy for Hunter disease: up to 9 years experience with 17 patients. Mol Genet Metab Rep. Jun 2015;3:65-74. doi:10.1016/j.ymgmr.2015.03.011
13. Scarpa M, Almássy Z, Beck M, et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis. 2011/11/07 2011;6(1):72. doi:10.1186/1750-1172-6-72
14. Janzen D, Delaney KA, Shapiro EG. Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: a review of the literature. Mol Genet Metab. Jun 2017;121(2):57-69. doi:10.1016/j.ymgme.2017.05.005
15. Mullen EM, American Guidance S. Mullen Scales of Early Learning. AGS ed ed. AGS Circle Pines, Minnesota; 1995.
16. Wheeler AC, Gwaltney A, Raspa M, et al. Emergence of developmental delay in infants and toddlers with an FMR1 mutation. Pediatrics. May 2021;147(5)doi:10.1542/peds.2020-011528
17. Cho Y, al. e. Beyond the normative data: understanding the Mullen Scales of Early Learning. ICIEM Virtual Congress. 2021.
18. Seo JH, Okuyama T, Shapiro E, Fukuhara Y, Kosuga M. Natural history of cognitive development in neuronopathic mucopolysaccharidosis type II (Hunter syndrome): contribution of genotype to cognitive developmental course. Mol Genet Metab Rep. Sep 2020;24:100630. doi:10.1016/j.ymgmr.2020.100630
19. Kim A, Poe M, Escolar M. Mullen Scales of Early Learning (MSEL) and Bayley Scales of Infant and Toddler Development (BSID): utility in assessing cognitive endpoints in MPS clinical trials. Mol Genet Metab. 2021;132(2):S55.
20. van der Lee JH, Morton J, Adams HR, et al. Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure. Mol Genet Metab. Jun 2017;121(2):70-79. doi:10.1016/j.ymgme.2017.05.004
21. Akshoomoff N. Use of the Mullen Scales of Early Learning for the assessment of young children with Autism Spectrum Disorders. Child Neuropsychol. Aug 2006;12(4-5):269-77. doi:10.1080/09297040500473714
22. Burns TG, King TZ, Spencer KS. Mullen scales of early learning: the utility in assessing children diagnosed with autism spectrum disorders, cerebral palsy, and epilepsy. Appl Neuropsychol Child. 2013;2(1):33-42. doi:10.1080/21622965.2012.682852