Adaptive skills in children with mucopolysaccharidoses

Introduction. Mucopolysaccharidoses (MPS) are a group of rare lethal lysosomal storage disoders. The progress in pathogenetic and symptomatic treatment, achieved in the last two decades, has resulted in increased life expectancy of patients. Assessment of functional abilities of patients is necessary for optimization of medical, psychological, and pedagogical support.

The aim of the study. To study the adaptive skills, measured with Vineland Adaptive Behavior Scales, and the impact of enzyme-replacement therapy on adaptive skills in MPS children.

Materials and methods. A semi-structured interview for Vineland Adaptive Behavior Scales filling was carried out with one of the parents of 59 children with MPS. 41 patients had neuronopathic disease: 20 children received pathogenetic еnzyme replacement therapy (ERT), 21 patients didn’t receive ERT. 18 patients exhibited non-neuronopathic disease: 8 children received ERT, 10 — didn’t receive pathogenetic therapy. Dynamical changes in adaptive skills were investigated in 11 patients with neuronopathic MPS.

Results. Low level of adaptive motor, communication, daily living and socialization skills and their dynamical regress, stagnation or decele­ration are characteristic for children with neuronopathic MPS. More than 75% of non-neuronopathic MPS patients have moderately low and low levels of adaptive behavior composite. ERT hasn’t demonstrated significant impact on adaptive skills in MPS patients. Non-significant tendency toward better level of communication skills has been noticed in children, receiving pathogenetic therapy. Necessity of weekly infusion may have a negative influence on patients’ socialization.

Conclusion. Elaboration of motor, pedagogical, and social rehabilitation programs is needed for correction of deficiency in adaptive skills and  achieving adequate social adaptation in MPS children with preserved cognitive abilities.

Contribution:
Osipova L.A. — concept, data collection, data processing and analysis, text writing, text editing;
Kuzenkova L.M. — concept, text editing; 
Podkletnova T.V. — concept, text editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgments. The study had no sponsorship.

Conflict of interest. The authors declare participation in educational activities with the support of Takeda Pharmaceutical Company.

Received: February 2, 2023
Accepted:  March 3, 2023
Published: April 20, 2023

1. Braunlin E.A. Cardiac Involvement in the Mucopolysaccharide Disoders. In: Moller J.H., Hoffman J.I.E., eds. Pediatric Cardiovascular Medicine. 2nd Edition. Wiley-Blackwell; 2012; 982–91.

2. Neufeld E., Muenzer J. The mucopolysaccharidosis. In: Scriver C.R., Beaudet A.L., Sly W.S., Valle D., eds. The Metabolic and Molecular Basis of Inherited Disease. New York: McGraw-Hill; 2001; 3421–52.

3. Lyon G., Kolodny E.H., Pastores G.M. Neurology of Hereditary Metabolic Disease of Children. 3rd edition. McGraw-Hill; 2006.

4. Saudubray J., van den Berghe J., Walter J.H., editors. Inborn Metabolic Diseases. 5th edition. Springer; 2012.

5. Wilkinson F.L., Holley R.J., Langford-Smith K.J., Badrinath S., Liao A., Langford-Smith A., et al. Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS One. 2012; 7(4): e35787. https://doi.org/10.1371/journal.pone.0035787

6. Zafeiriou D.I., Batzios S.P. Brain and spinal MR imaging findings in mucopolysaccharidoses: a review. AJNR Am. J. Neuroradiol. 2013; 34(1): 5–13. https://doi.org/10.3174/ajnr.A2832

7. Giugliani R., Federhen S., Bittar C., Souza N.C., Quoos M.F., Baldo M.U. Emerging treatment options for the mucopolysaccharidoses. Res. Rep. Endocr. Disord. 2012; 2: 53–64. https://doi.org/10.2147/RRED.S24769

8. Barone R., Pellico A., Pittalà A., Gasperini S. Neurobehavioral phenotypes of neuronopathic mucopolysaccharidoses. Ital. J. Pediatr. 2018; 44(Suppl. 2): 121. https://doi.org/10.1186/s13052-018-0561-2

9. Mehta A., Winchester B., editors. Lysosomal Storage Disease: A Practical Guide. New York: Wiley-Blackwell; 2012.

10. Holt J.B., Poe M.D., Escolar M.L. Natural progression of neurological disease in mucopolysaccharidosis type II. Pediatrics. 2011; 127(5): e1258-65. https://doi.org/10.1542/peds.2010-1274

11. Barranger J.A., Cabrera-Salazar M.A. Lysosomal Storage Disorders. Berlin: Springer; 2007.

12. Muenzer J., Beck M., Eng C.M., Escolar M.L., Giugliani R., Guffon N.H., et al. Multidisciplinary management of Hunter syndrome. Pediatrics. 2009; 124(6): e1228–39. https://doi.org/10.1542/peds.2008-0999

13. Arfi A., Richard M., Scherman D. Innovative Therapeutic Approaches for Improving Patient Life Condition with a Neurological Lysosomal Disease; 2012. Available at: http://www.intechopen.com/books/latest-findings-in-intellectual-and-developmental-disabilities-research/innovative-therapeutic-approaches-for-improving-patient-life-condition-with-a-neurological-lysosomal

14. Valstar M.J., Marchal J.P., Grootenhuis M., Colland V., Wijburg F.A. Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome). Orphanet. J. Rare Dis. 2011; 6: 43. https://doi.org/10.1186/1750-1172-6-43

15. Wijburg F.A., Węgrzyn G., Burton B.K., Tylki-Szymańska A. Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta. Paediatr. 2013; 102(5): 462–70. https://doi.org/10.1111/apa.12169

16. Bjoraker K.J., Delaney K., Peters C., Krivit W., Shapiro E.G. Long-term outcomes of adaptive functions for children with mucopolysaccharidosis I (Hurler syndrome) treated with hematopoietic stem cell transplantation. J. Dev. Behav. Pediatr. 2006; 27(4): 290–6. https://doi.org/10.1097/00004703-200608000-00002

17. Raluy-Callado M., Chen W.H., Whiteman D.A., Fang J., Wiklund I. The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life. Orphanet. J. Rare Dis. 2013; 8: 101. https://doi.org/10.1186/1750-1172-8-101

18. Sparrow S.S., Balla D.A., Cicchetti D.V. The Vineland Adaptive Behavior Scales: Interview Edition, Survey Form. Circle Pines, MN: American Guidance Service; 1984.

19. Delaney K.A., Rudser K.R., Yund B.D., Whitley C.B., Haslett P.A., Shapiro E.G. Methods of neurodevelopmental assessment in children with neurodegenerative disease: Sanfilippo syndrome. JIMD Rep. 2014; 13: 129–37. https://doi.org/10.1007/8904_2013_269

20. van der Lee J.H., Morton J., Adams H.R., Clarke L., Ebbink B.J., Escolar M.L., et al. Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure. Mol. Genet. Metab. 2017; 121(2): 70–9. https://doi.org/10.1016/j.ymgme.2017.05.004

21. Applied Statistics for a Doctor. Primary Data Analysis. Methodological Developments [Prikladnaya statistika dlya vracha. Pervichnyy analiz dannykh. Metodicheskie razrabotki]. Moscow; 2008. (in Russian)

22. Rebrova O.Yu. Statistical Analysis of Medical Data. Application of the Package of Applied Programs STATISTICA [Statisticheskiy analiz meditsinskikh dannykh. Primenenie paketa prikladnykh programm STATISTICA]. Moscow: Media Sfera; 2002. (in Russian)

23. Trukhacheva N.V. Mathematical Statistics in Biomedical Research Using the Package Statistica [Matematicheskaya statistika v mediko-biologicheskikh issledovaniyakh s primeneniem paketa Statistica]. Moscow: GEOTAR-Media; 2013. (in Russian)

24. Needham M., Packman W., Rappoport M., Quinn N., Cordova M., Macias S., et al. MPS II: adaptive behavior of patients and impact on the family system. J. Genet. Couns. 2014; 23(3): 330–8. https://doi.org/10.1007/s10897-013-9665-4

25. Whitley C.B., Cleary M., Eugen Mengel K., Harmatz P., Shapiro E., Nestrasil I., et al. Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B. J. Pediatr. 2018; 197: 198–206.e2. https://doi.org/10.1016/j.jpeds.2018.01.044

26. Truxal K.V., Fu H., McCarty D.M., McNally K.A., Kunkler K.L., Zumberge N.A., et al. A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: Implications for clinical trial design. Mol. Genet. Metab. 2016; 119(3): 239–48. https://doi.org/10.1016/j.ymgme.2016.08.002

27. Shapiro E., Ahmed A., Whitley C., Delaney K. Observing the advanced disease course in mucopolysaccharidosis, type IIIA; a case series. Mol. Genet. Metab. 2018; 123(2): 123–6. https://doi.org/10.1016/j.ymgme.2017.11.014

28. Shapiro E.G., Rudser K., Ahmed A., Steiner R.D., Delaney K.A., Yund B., et al. A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II. Mol. Genet. Metab. Rep. 2016; 7: 32–9. https://doi.org/10.1016/j.ymgmr.2016.03.005

29. Shapiro E.G., Nestrasil I., Rudser K., Delaney K., Kovac V., Ahmed A., et al. Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment. Mol. Genet. Metab. 2015; 116(1-2): 61–8. https://doi.org/10.1016/j.ymgme.2015.06.002