neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2023-4-1-6-14bolixbneurojour-83Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSАдаптивные навыки детей с мукополисахаридозамиAdaptive skills in children with mucopolysaccharidoseshttps://orcid.org/0000-0002-6545-4121ОсиповаЛилия АлександровнаOsipovaLiliya A.

Невролог консультативного отделения консультативно-диагностического центра ФГАУ «НМИЦ здоровья детей», 119991, Москва.

e-mail: liliya-o@yandex.ru

Neurologist of сonsultative department of Consultative and diagnostic center, National Medical Research Center of Children’s Health, Moscow, 119991, Russian Federation.

e-mail: liliya-o@yandex.ru

liliya-o@yandex.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛюдмила М.KuzenkovaLudmila M.noemail@neicon.ruhttps://orcid.org/0000-0001-6415-156XПодклетноваТатьяна В.PodkletnovaTatyana V.noemail@neicon.ruФГАУ «Научный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center of Children’s HealthRussian FederationФГАУ «Научный медицинский исследовательский центр здоровья детей» Минздрава России; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияNational Medical Research Center of Children’s Health; I.M. Sechenov First Moscow State Medical UniversityRussian Federation20231205202341614Copyright © Осипова Л.А., Кузенкова Л.М., Подклетнова Т.В., 20232023Осипова Л.А., Кузенкова Л.М., Подклетнова Т.В.Osipova L.A., Kuzenkova L.M., Podkletnova T.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/83Введение

Введение. Мукополисахаридозы (МПС) — группа редких летальных лизосомных болезней накопления. Произошедший в последние два десятилетия прогресс в патогенетическом и симптоматическом лечении МПС привёл к увеличению продолжительности жизни пациентов. Для оптимизации медицинской и психолого-педагогической помощи в условиях новых подходов к лечению МПС необходимы исследование и оценка функциональных возможностей больных.

Цель исследования — изучение адаптивных навыков и влияния на них ферментозаместительной терапии (ФЗТ) у детей с МПС с использованием шкалы адаптивного поведения Вайнленд.

Материалы и методы

Материалы и методы. Полуструктурированное интервью для заполнения шкалы Вайнденд было проведено с одним из родителей 59 детей с МПС: 41 пациент с нейронопатическим вариантом течения МПС (20 детей получали патогенетическую ФЗТ, 21 — не получал); 18 пациентов с ненейронопатическим вариантом течения МПС (8 детей получали ФЗТ, 10 — не получали). Исследование динамических изменений адаптивных навыков выполнено у 11 пациентов с нейронопатическим течением МПС. 

Результаты

Результаты. Для детей с нейронопатическими МПС характерны низкий уровень и динамический регресс, стагнация или замедление приобретения моторных, коммуникативных, повседневных и социальных навыков. Более 75% пациентов с ненейронопатическими МПС имеют средние низкие или низкие уровни составного показателя адаптивного поведения. ФЗТ не продемонстрировала значимого влияния на показатели адаптивных функций пациентов с МПС. У детей, получающих патогенетическое лечение, отмечена статистически незначимая тенденция к лучшему уровню коммуникативных навыков. Необходимость еженедельного проведения лечебных инфузий может оказывать негативное влияние на социализацию пациентов. 

Заключение

Заключение. Для коррекции имеющегося дефицита адаптивных навыков и, соответственно, для достижения адекватной социальной адаптации пациентов с МПС, имеющих сохранный интеллект, необходима разработка программ двигательной, педагогической и социальной реабилитации. 

Участие авторов

Участие авторов:Осипова Л.А. — концепция, сбор данных, обработка и анализ полученных данных, написание текста, редактирование текста;Кузенкова Л.М. — концепция, редактирование текста;Подклетнова Т.В. — концепция, редактирование текста.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи и за информацию об авторах.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Конфликт интересов

Конфликт интересов. Все авторы участвовали в образовательных обучающих мероприятиях при поддержке ООО «Такеда Фармасьютикалс».

Поступила 20

Поступила 20.02.2023Принята к печати 03.03.2023Опубликована 20.04.2023 

Introduction

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

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

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

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

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

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

Acknowledgments. The study had no sponsorship.

Conflict of interest

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

Received

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

мукополисахаридозыадаптивные навыкишкала адаптивного поведения Вайндендреабилитациясоциальная адаптацияmucopolysaccharidosesadaptive skillsVineland Adaptive Behavior Scalesrehabilitationsocial adaptationReferencesBraunlin 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.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.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.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.Lyon G., Kolodny E.H., Pastores G.M. Neurology of Hereditary Metabolic Disease of Children. 3rd edition. McGraw-Hill; 2006.Lyon G., Kolodny E.H., Pastores G.M. Neurology of Hereditary Metabolic Disease of Children. 3rd edition. McGraw-Hill; 2006.Saudubray J., van den Berghe J., Walter J.H., editors. Inborn Metabolic Diseases. 5th edition. Springer; 2012.Saudubray J., van den Berghe J., Walter J.H., editors. Inborn Metabolic Diseases. 5th edition. Springer; 2012.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.0035787Wilkinson 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.0035787Zafeiriou 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.A2832Zafeiriou 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.A2832Giugliani 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.S24769Giugliani 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.S24769Barone 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/s13052-018-0561-2Barone 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/s13052-018-0561-2Mehta A., Winchester B., editors. Lysosomal Storage Disease: A Practical Guide. New York: Wiley-Blackwell; 2012.Mehta A., Winchester B., editors. Lysosomal Storage Disease: A Practical Guide. New York: Wiley-Blackwell; 2012.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.2010-1274Holt 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.2010-1274Barranger J.A., Cabrera-Salazar M.A. Lysosomal Storage Disorders. Berlin: Springer; 2007.Barranger J.A., Cabrera-Salazar M.A. Lysosomal Storage Disorders. Berlin: Springer; 2007.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.2008-0999Muenzer 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.2008-0999Arfi 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-lysosomalArfi 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-lysosomalValstar 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/10.1186/1750-1172-6-43Valstar 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/10.1186/1750-1172-6-43Wijburg 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.12169Wijburg 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.12169Bjoraker 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/10.1097/00004703-200608000-00002Bjoraker 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/10.1097/00004703-200608000-00002Raluy-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/10.1186/1750-1172-8-101Raluy-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/10.1186/1750-1172-8-101Sparrow S.S., Balla D.A., Cicchetti D.V. The Vineland Adaptive Behavior Scales: Interview Edition, Survey Form. Circle Pines, MN: American Guidance Service; 1984.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.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_269Delaney 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_269van 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.2017.05.004van 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.2017.05.004Прикладная статистика для врача. Первичный анализ данных. Методические разработки. M.; 2008.Applied Statistics for a Doctor. Primary Data Analysis. Methodological Developments [Prikladnaya statistika dlya vracha. Pervichnyy analiz dannykh. Metodicheskie razrabotki]. Moscow; 2008. (in Russian)Реброва О.Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA. M.: Медиа Сфера; 2002.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)Трухачёва Н.В. Математическая статистика в медико-биологических исследованиях с применением пакета Statistica. M.: ГЭОТАР-Медиа; 2013.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)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/s10897-013-9665-4Needham 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/s10897-013-9665-4Whitley 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.2018.01.044Whitley 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.2018.01.044Truxal 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.2016.08.002Truxal 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.2016.08.002Shapiro 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.2017.11.014Shapiro 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.2017.11.014Shapiro 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.2016.03.005Shapiro 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.2016.03.005Shapiro 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.2015.06.002Shapiro 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

The authors declare that there are no conflicts of interest present.