neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2023-4-3-144-157bbiapkneurojour-106Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL CASESБессимптомное повышение тропонина I и острый миокардит в отсроченном периоде генозаместительной терапии онасемногеном аберпавовеком у пациентов со спинальной мышечной атрофией: обзор литературы и серия клинических случаевAsymptomatic troponin I elevation and acute myocarditis in the late period of gene replacement therapy with onasemnogene aberpavovec for patients with spinal muscular atrophy: literature review and clinical case serieshttps://orcid.org/0000-0003-3794-6855ПапинаЮлия ОлеговнаPapinaYuliya O.

Врач-невролог отделения психоневрологии ФГБУ «НИИ педиатрии и детской хирургии им. В.В. Вельтищева» ФГАОУ ВО РНИМУ им. Н.И. Пирогова, 125412, Москва.

e-mail: papina.u@pedklin.ru

Neurologist of the Department of Psycho-neurology, Veltishchev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University, Moscow, 125412, Russian Federation.

e-mail: papina.u@pedklin.ru

papina.u@pedklin.ruhttps://orcid.org/0000-0002-8876-7462АртемьеваСветлана Б.ArtemyevaSvetlana B.noemail@neicon.ruhttps://orcid.org/0000-0002-7511-3240ГрозноваОльга С.GroznovaOlga S.noemail@neicon.ruhttps://orcid.org/0009-0007-6195-3402ЛукьяноваИнна В.LukyanovaInna V.noemail@neicon.ruhttps://orcid.org/0000-0001-5436-836XМельникЕвгения А.MelnikEvgeniya A.noemail@neicon.ruhttps://orcid.org/0009-0003-4418-0269ТутельманКонстантин М.TutelmanKonstantin M.noemail@neicon.ruhttps://orcid.org/0000-0003-2635-2752ВлодавецДмитрий В.VlodavetsDmitrii V.noemail@neicon.ruОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии имени академика Ю.Е. Вельтищева» ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical UniversityRussian Federation20231910202343144157Copyright © Папина Ю.О., Артемьева С.Б., Грознова О.С., Лукьянова И.В., Мельник Е.А., Тутельман К.М., Влодавец Д.В., 20232023Папина Ю.О., Артемьева С.Б., Грознова О.С., Лукьянова И.В., Мельник Е.А., Тутельман К.М., Влодавец Д.В.Papina Y.O., Artemyeva S.B., Groznova O.S., Lukyanova I.V., Melnik E.A., Tutelman K.M., Vlodavets D.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/106Введение

Введение. Спинальная мышечная атрофия (СМА) 5q — редкое генетически обусловленное прогрессирующее нервно-мышечное заболевание, являвшееся до недавнего времени наиболее частой причиной младенческой смертности. В настоящее время в клинической практике успешно используется один из видов патогенетической терапии данного заболевания — препарат онасемноген абепарвовек (ОА). Генная заместительная терапия (ГЗТ) с применением ОА у пациентов с СМА может сопровождаться изменениями со стороны сердечно-сосудистой системы, что требует своевременной диагностики и мониторинга.

Цель — представить серию клинических наблюдений детей с генетически подтверждённой СМА и повышением уровня тропонина I после проведения ГЗТ ОА.

Материалы и методы

Материалы и методы. В детском неврологическом отделении под наблюдением находились 42 ребёнка с генетически подтверждённой СМА, получивших ГЗТ ОА. Всем проводилось исследование тропонина I до и после инфузии, по показаниям — дополнительное определение промозгового натрийуретического пептида (NT-proBNP), креатинфосфокиназы-МВ (КФК-МВ), электрокардиографическое и эхокардиографическое обследования.

Результаты

Результаты. У 11 (26,2%) из 42 включённых в исследование детей с СМА выявлено повышение уровня тропонина I в крови, которое определялось до 8-й недели после введения препарата. При этом повышенная концентрация тропонина I в большинстве случаев (у 41 детей из 42) не сопровождалась клинически значимыми проявлениями. Только в 1 случае у девочки при длительно (10 мес) сохраняющемся повышении уровня тропонина I на фоне интеркуррентной инфекции развился острый миокардит, подтверждённый клиническими и инструментальными методами исследования.

Заключение

Заключение. Повышение уровня тропонина I, выявляемое после проведения ГЗТ ОА у больных СМА, чаще остаётся бессимптомным. Описанный нами случай миокардита свидетельствует о необходимости более продолжительного мониторинга состояния сердечной мышцы при повышении тропонина I, особенно на фоне интеркуррентных бактериально-вирусных инфекций.

Соблюдение этических норм. Исследование одобрено локальным этическим комитетом ФГАОУ ВО РНИМУ им. Пирогова, Москва, 117997 (протокол № 226 от 20.02.2023).

Участие авторов

Участие авторов:Папина Ю.О. — дизайн исследования, координация исследования, сбор материала и обработка данных, написание текста, обзор публикаций по теме статьи;Артемьева С.Б. — координация исследования, получение данных для анализа, анализ полученных данных, редактирование статьи;Грознова О.С. — получение данных для анализа, анализ полученных данных, написание текста;Лукьянова И.В. — получение данных для анализа, анализ полученных данных, написание текста;Мельник Е.А. — анализ полученных данных, редактирование статьи;Тутельман К.М. — получение данных для анализа, редактирование статьи;Влодавец Д.В. — координация исследования, редактирование статьи.

Благодарности

Благодарности. Исследование не имело спонсорской поддержки.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Поступила 26

Поступила 26.06.2023Принята к печати 30.08.2023Опубликована 13.10.2023

Introduction

Introduction. Spinal muscular atrophy (SMA) 5q is a rare genetically determined progressive neuromuscular disorder, is the most frequent cause of infant death not long ago. Nowadays onasemnogen abeparvovec as pathogenetic therapy is successfully used in clinical practice to combat this disease. Gene replacement therapy (GRT) with onasemnogen abeparvovec for SMA patients may come amid non-target changes in the cardiovascular system that require early diagnosis and monitoring.

Objective

Objective. To present clinical reports considering children with genetically confirmed SMA and elevated troponin I levels after onasemnogen abeparvovec gene replacement therapy.

Materials and methods

Materials and methods. We monitored forty two children with genetically confirmed SMA who received gene replacement therapy with onasemnogen abeparvovec in the pediatric neurology department. All patients were tested for troponin I before and after the infusion, additional tests of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), creatine phosphokinase-MB (CPK-MB), electrocardiogram, echocardiography were made if needed.

Results

Results. In 11 (26.2%) of 42 SMA children troponin I was elevated and detected up to the eighth week after drug administration. At the same time, an increased concentration of troponin I in the majority of cases (41 out of 42 children) was not associated with clinically significant manifestations. There was only one case when acute myocarditis, confirmed by clinical and instrumental methods of investigation occurred. It was a girl with a long-term (10 months) elevation of troponin I, who had an intercurrent infection.

Conclusions

Conclusions. Troponin I elevations detected after GRT with onasomnogene abeparvovec in SMA patients are often asymptomatic. This myocarditis case highlights the importance of longer cardiac monitoring of troponin I elevations, especially in the presence of intercurrent bacterial and viral infections.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the Pirogov Russian National Research Medical University, Ostrovitianov str. 1, Moscow, 117997, Russia (Protoсol No. 226 of 20.02.2023).

Contribution

Contribution:Papina Y.O. — research design, coordination of the study, material collection and data processing, text writing, review of publications on the topic of the articleArtemyeva S.B. — coordination of the study, obtaining data for analysis, analyzing the data obtained, article editingGroznova O.S. — obtaining data for analysis, analyzing the data obtained, text writingLukyanova I.V. — obtaining data for analysis, analyzing the data obtained, text writingMelnik E.A. — analyzing the data obtained, article editingTutelman K.M. — obtaining data for analysis, article editingVlodavets D.V. — coordination of the study, article editing

Acknowledgements

Acknowledgements. The study had no sponsorship.

Conflict of interest

Conflict of interest. The authors declare no conflict of interest.

Received

Received: June 26, 2023Accepted: August 30, 2023Published: October 13, 2023

генозаместительная терапияонасемноген абепарвовеквоспалительная кардиомиопатиямиокардиттропонинспинальная мышечная атрофиясердцеSMN1белок SMNgene replacement therapyonasemnogen abeparvovecinflammatory cardiomyopathymyocarditistroponinspinal muscular atrophyheartSMN1SMN proteinReferencesDarras B.T. Spinal muscular atrophies. Pediatr. Clin. North Am. 2015; 62(3): 743–66. https://doi.org/10.1016/j.pcl.2015.03.010Darras B.T. Spinal muscular atrophies. Pediatr. Clin. North Am. 2015; 62(3): 743–66. https://doi.org/10.1016/j.pcl.2015.03.010Kolb S.J., Kissel J.T. Spinal muscular atrophy. Neurol. Clin. 2015; 33(4): 831–46. https://doi.org/10.1016/j.ncl.2015.07.004Kolb S.J., Kissel J.T. Spinal muscular atrophy. Neurol. Clin. 2015; 33(4): 831–46. https://doi.org/10.1016/j.ncl.2015.07.004Verhaart I.E.C., Robertson A., Wilson I.J., Aartsma-Rus A., Cameron S., Jones C.C., et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J. Rare Dis. 2017; 12(1): 124. https://doi.org/10.1186/s13023-017-0671-8Verhaart I.E.C., Robertson A., Wilson I.J., Aartsma-Rus A., Cameron S., Jones C.C., et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J. Rare Dis. 2017; 12(1): 124. https://doi.org/10.1186/s13023-017-0671-8D’Amico A., Mercuri E., Tiziano F.D., Bertini E. Spinal muscular atrophy. Orphanet J. Rare Dis. 2011; 6(1): 1–10. https://doi.org/10.1186/1750-1172-6-71D’Amico A., Mercuri E., Tiziano F.D., Bertini E. Spinal muscular atrophy. Orphanet J. Rare Dis. 2011; 6(1): 1–10. https://doi.org/10.1186/1750-1172-6-71Mikhalchuk K., Shchagina O., Chukhrova A., Zabnenkova V., Chausova P., Ryadninskaya N., et al. Pilot program of newborn screening for 5q spinal muscular atrophy in the Russian Federation. Int. J. Neonatal Screen. 2023; 9(2): 29. https://doi.org/10.3390/ijns9020029Mikhalchuk K., Shchagina O., Chukhrova A., Zabnenkova V., Chausova P., Ryadninskaya N., et al. Pilot program of newborn screening for 5q spinal muscular atrophy in the Russian Federation. Int. J. Neonatal Screen. 2023; 9(2): 29. https://doi.org/10.3390/ijns9020029Hjartarson H.T., Nathorst-Böös K., Sejersen T. Disease modifying therapies for the management of children with spinal muscular atrophy (5q SMA): an update on the emerging evidence. Drug Des. Devel. Ther. 2022; 16: 1865–83. https://doi.org/10.2147/dddt.s214174Hjartarson H.T., Nathorst-Böös K., Sejersen T. Disease modifying therapies for the management of children with spinal muscular atrophy (5q SMA): an update on the emerging evidence. Drug Des. Devel. Ther. 2022; 16: 1865–83. https://doi.org/10.2147/dddt.s214174Finkel R.S., Mercuri E., Darras B.T., Connolly A.M., Kuntz N.L., Kirschner J., et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med. 2017; 377(18): 1723–32. https://doi.org/10.1056/nejmoa1702752Finkel R.S., Mercuri E., Darras B.T., Connolly A.M., Kuntz N.L., Kirschner J., et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med. 2017; 377(18): 1723–32. https://doi.org/10.1056/nejmoa1702752Dhillon S. Risdiplam: first approval. Drugs. 2020; 80(17): 1853–8. https://doi.org/10.1007/s40265-020-01410-zDhillon S. Risdiplam: first approval. Drugs. 2020; 80(17): 1853–8. https://doi.org/10.1007/s40265-020-01410-zMendell J.R., Al-Zaidy S., Shell R., Arnold W.D., Rodino-Klapac L.R., Prior T.W., et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 2017; 377(18): 1713–22. https://doi.org/10.1056/nejmoa1706198Mendell J.R., Al-Zaidy S., Shell R., Arnold W.D., Rodino-Klapac L.R., Prior T.W., et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 2017; 377(18): 1713–22. https://doi.org/10.1056/nejmoa1706198Day J.W., Finkel R.S., Chiriboga C.A., Connolly A.M., Crawford T.O., Darras B.T., et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021; 20(4): 284–93. https://doi.org/10.1016/s1474-4422(21)00001-6Day J.W., Finkel R.S., Chiriboga C.A., Connolly A.M., Crawford T.O., Darras B.T., et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021; 20(4): 284–93. https://doi.org/10.1016/s1474-4422(21)00001-6Novartis. Novartis shares Zolgensma long-term data demonstrating sustained durability up to 7.5 years post-dosing; 100% achievement of all assessed milestones in children treated prior to SMA symptom onset. Available at: https://www.novartis.com/news/media-releases/novartis-shares-zolgensma-long-term-data-demonstrating-sustained-durability-75-years-post-dosing-100-achievement-all-assessed-milestones-children-treated-prior-sma-symptom-onsetNovartis. Novartis shares Zolgensma long-term data demonstrating sustained durability up to 7.5 years post-dosing; 100% achievement of all assessed milestones in children treated prior to SMA symptom onset. Available at: https://www.novartis.com/news/media-releases/novartis-shares-zolgensma-long-term-data-demonstrating-sustained-durability-75-years-post-dosing-100-achievement-all-assessed-milestones-children-treated-prior-sma-symptom-onsetZiegler A., Wilichowski E., Schara U., Hahn A., Müller-Felber W., Johannsen J., et al. Recommendations for gene therapy of spinal muscular atrophy with onasemnogene abeparvovec-AVXS-101: Consensus paper of the German representatives of the Society for Pediatric Neurology (GNP) and the German treatment centers with collaboration of the medic. Nervenarzt. 2020; 91(6): 518–29. https://doi.org/10.1007/s00115-020-00919-8 (in German)Ziegler A., Wilichowski E., Schara U., Hahn A., Müller-Felber W., Johannsen J., et al. Recommendations for gene therapy of spinal muscular atrophy with onasemnogene abeparvovec-AVXS-101: Consensus paper of the German representatives of the Society for Pediatric Neurology (GNP) and the German treatment centers with collaboration of the medic. Nervenarzt. 2020; 91(6): 518–29. https://doi.org/10.1007/s00115-020-00919-8 (in German)Day J.W., Mendell J.R., Mercuri E., Finkel R.S., Strauss K.A., Kleyn A., et al. Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy. Drug Saf. 2021; 44(10): 1109–19. https://doi.org/10.1007/s40264-021-01107-6Day J.W., Mendell J.R., Mercuri E., Finkel R.S., Strauss K.A., Kleyn A., et al. Clinical trial and postmarketing safety of onasemnogene abeparvovec therapy. Drug Saf. 2021; 44(10): 1109–19. https://doi.org/10.1007/s40264-021-01107-6Strauss K.A., Farrar M.A., Muntoni F., Saito K., Mendell J.R., Servais L., et al. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial. Nat. Med. 2022; 28(7): 1390–7. https://doi.org/10.1038/s41591-022-01867-3Strauss K.A., Farrar M.A., Muntoni F., Saito K., Mendell J.R., Servais L., et al. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial. Nat. Med. 2022; 28(7): 1390–7. https://doi.org/10.1038/s41591-022-01867-3Blair H.A. Onasemnogene abeparvovec: A review in spinal muscular atrophy. CNS Drugs. 2022; 36(9): 995–1005. https://doi.org/10.1007/s40263-022-00941-1Blair H.A. Onasemnogene abeparvovec: A review in spinal muscular atrophy. CNS Drugs. 2022; 36(9): 995–1005. https://doi.org/10.1007/s40263-022-00941-1Chand D.H., Sun R., Diab K.A., Kenny D., Tukov F.F. Review of cardiac safety in onasemnogene abeparvovec gene therapy: translation from preclinical to clinical findings. Res. Sq. 2022. Preprint. https://doi.org/10.21203/rs.3.rs-1979632/v1Chand D.H., Sun R., Diab K.A., Kenny D., Tukov F.F. Review of cardiac safety in onasemnogene abeparvovec gene therapy: translation from preclinical to clinical findings. Res. Sq. 2022. Preprint. https://doi.org/10.21203/rs.3.rs-1979632/v1Friese J., Geitmann S., Holzwarth D., Müller N., Sassen R., Baur U., et al. Safety monitoring of gene therapy for spinal muscular atrophy with onasemnogene abeparvovec – a single centre experience. J. Neuromuscul. Dis. 2021; 8(2): 209–16. https://doi.org/10.3233/jnd-200593Friese J., Geitmann S., Holzwarth D., Müller N., Sassen R., Baur U., et al. Safety monitoring of gene therapy for spinal muscular atrophy with onasemnogene abeparvovec – a single centre experience. J. Neuromuscul. Dis. 2021; 8(2): 209–16. https://doi.org/10.3233/jnd-200593Ali H.G., Ibrahim K., Elsaid M.F., Mohamed R.B., Abeidah M.I.A., Al Rawwas A.O., et al. Gene therapy for spinal muscular atrophy: the Qatari experience. Gene Ther. 2021; 28(10-11): 676–80. https://doi.org/10.1038/s41434-021-00273-7Ali H.G., Ibrahim K., Elsaid M.F., Mohamed R.B., Abeidah M.I.A., Al Rawwas A.O., et al. Gene therapy for spinal muscular atrophy: the Qatari experience. Gene Ther. 2021; 28(10-11): 676–80. https://doi.org/10.1038/s41434-021-00273-7Bitetti I., Lanzara V., Margiotta G., Varone A. Onasemnogene abeparvovec gene replacement therapy for the treatment of spinal muscular atrophy: a real-world observational study. Gene Ther. 2023; 30(7-8): 592–7. https://doi.org/10.1038/s41434-022-00341-6Bitetti I., Lanzara V., Margiotta G., Varone A. Onasemnogene abeparvovec gene replacement therapy for the treatment of spinal muscular atrophy: a real-world observational study. Gene Ther. 2023; 30(7-8): 592–7. https://doi.org/10.1038/s41434-022-00341-6D’Silva A.M., Holland S., Kariyawasam D., Herbert K., Barclay P., Cairns A., et al. Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. Ann. Clin. Transl. Neurol. 2022; 9(3): 339–50. https://doi.org/10.1002/acn3.51519D’Silva A.M., Holland S., Kariyawasam D., Herbert K., Barclay P., Cairns A., et al. Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. Ann. Clin. Transl. Neurol. 2022; 9(3): 339–50. https://doi.org/10.1002/acn3.51519Stettner G.M., Hasselmann O., Tscherter A., Galiart E., Jacquier D., Klein A. Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study. BMC Neurol. 2023; 23(1): 88. https://doi.org/10.1186/s12883-023-03133-6Stettner G.M., Hasselmann O., Tscherter A., Galiart E., Jacquier D., Klein A. Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study. BMC Neurol. 2023; 23(1): 88. https://doi.org/10.1186/s12883-023-03133-6Weiß C., Ziegler A., Becker L.L., Johannsen J., Brennenstuhl H., Schreiber G., et al. Gene replacement therapy with onasemnogene abeparvovec in children with spinal muscular atrophy aged 24 months or younger and bodyweight up to 15 kg: an observational cohort study. Lancet Child Adolesc. Heal. 2022; 6(1): 17–27. https://doi.org/10.1016/s2352-4642(21)00287-xWeiß C., Ziegler A., Becker L.L., Johannsen J., Brennenstuhl H., Schreiber G., et al. Gene replacement therapy with onasemnogene abeparvovec in children with spinal muscular atrophy aged 24 months or younger and bodyweight up to 15 kg: an observational cohort study. Lancet Child Adolesc. Heal. 2022; 6(1): 17–27. https://doi.org/10.1016/s2352-4642(21)00287-xKarlén J., Karlsson M., Eliasson H., Bonamy A.E., Halvorsen C.P. Cardiac troponin T in healthy full-term infants. Pediatr. Cardiol. 2019; 40(8): 1645–54. https://doi.org/10.1007/s00246-019-02199-9Karlén J., Karlsson M., Eliasson H., Bonamy A.E., Halvorsen C.P. Cardiac troponin T in healthy full-term infants. Pediatr. Cardiol. 2019; 40(8): 1645–54. https://doi.org/10.1007/s00246-019-02199-9Yoldaş T., Örün U.A. What is the significance of elevated troponin I in children and adolescents? A diagnostic approach. Pediatr. Cardiol. 2019; 40(8): 1638–44. https://doi.org/10.1007/s00246-019-02198-wYoldaş T., Örün U.A. What is the significance of elevated troponin I in children and adolescents? A diagnostic approach. Pediatr. Cardiol. 2019; 40(8): 1638–44. https://doi.org/10.1007/s00246-019-02198-wDjordjevic S.A., Milic-Rasic V., Brankovic V., Kosac A., Vukomanovic G., Topalovic M., et al. Cardiac findings in pediatric patients with spinal muscular atrophy types 2 and 3. Muscle Nerve. 2021; 63(1): 75–83. https://doi.org/10.1002/mus.27088Djordjevic S.A., Milic-Rasic V., Brankovic V., Kosac A., Vukomanovic G., Topalovic M., et al. Cardiac findings in pediatric patients with spinal muscular atrophy types 2 and 3. Muscle Nerve. 2021; 63(1): 75–83. https://doi.org/10.1002/mus.27088Rittoo D., Jones A., Lecky B., Neithercut D. Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: Implications for the diagnosis of myocardial infarction. J. Am. Coll. Cardiol. 2014; 63(22): 2411–20. https://doi.org/10.1016/j.jacc.2014.03.027Rittoo D., Jones A., Lecky B., Neithercut D. Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: Implications for the diagnosis of myocardial infarction. J. Am. Coll. Cardiol. 2014; 63(22): 2411–20. https://doi.org/10.1016/j.jacc.2014.03.027Pierzchlewicz K., Kępa I., Podogrodzki J., Kotulska K. Spinal muscular atrophy: the use of functional motor scales in the era of disease-modifying treatment. Child Neurol. Open. 2021; 8: 2329048X211008725. https://doi.org/10.1177/2329048x211008725Pierzchlewicz K., Kępa I., Podogrodzki J., Kotulska K. Spinal muscular atrophy: the use of functional motor scales in the era of disease-modifying treatment. Child Neurol. Open. 2021; 8: 2329048X211008725. https://doi.org/10.1177/2329048x211008725Shababi M., Habibi J., Yang H.T., Vale S.M., Sewell W.A., Lorson C.L. Cardiac defects contribute to the pathology of spinal muscular atrophy models. Hum. Mol. Genet. 2010; 19(20): 4059–71. https://doi.org/10.1093/hmg/ddq329Shababi M., Habibi J., Yang H.T., Vale S.M., Sewell W.A., Lorson C.L. Cardiac defects contribute to the pathology of spinal muscular atrophy models. Hum. Mol. Genet. 2010; 19(20): 4059–71. https://doi.org/10.1093/hmg/ddq329Wijngaarde C.A., Blank A.C., Stam M., Wadman R.I., van den Berg L.H., van der Pol W.L. Cardiac pathology in spinal muscular atrophy: a systematic review. Orphanet J. Rare Dis. 2017; 12(1): 67. https://doi.org/10.1186/s13023-017-0613-5Wijngaarde C.A., Blank A.C., Stam M., Wadman R.I., van den Berg L.H., van der Pol W.L. Cardiac pathology in spinal muscular atrophy: a systematic review. Orphanet J. Rare Dis. 2017; 12(1): 67. https://doi.org/10.1186/s13023-017-0613-5Franklin R.C., Jacobs J.P., Krogmann O.N., Béland M.J., Aiello V.D., Colan S.D., et al. Nomenclature for congenital and paediatric cardiac disease: historical perspectives and The International Pediatric and Congenital Cardiac Code. Cardiol. Young. 2008; 18(Suppl. 2): 70–80. https://doi.org/10.1017/s1047951108002795Franklin R.C., Jacobs J.P., Krogmann O.N., Béland M.J., Aiello V.D., Colan S.D., et al. Nomenclature for congenital and paediatric cardiac disease: historical perspectives and The International Pediatric and Congenital Cardiac Code. Cardiol. Young. 2008; 18(Suppl. 2): 70–80. https://doi.org/10.1017/s1047951108002795Tanaka H., Nishi S., Nuruki K., Tanaka N. Myocardial ultrastructural changes in Kugelberg-Welander syndrome. Br. Heart J. 1977; 39(12): 1390–3. https://doi.org/10.1136/hrt.39.12.1390Tanaka H., Nishi S., Nuruki K., Tanaka N. Myocardial ultrastructural changes in Kugelberg-Welander syndrome. Br. Heart J. 1977; 39(12): 1390–3. https://doi.org/10.1136/hrt.39.12.1390Kuru S., Sakai M., Konagaya M., Yoshida M., Hashizume Y., Saito K. An autopsy case of spinal muscular atrophy type III (Kugelberg-Welander disease). Neuropathology. 2009; 29(1): 63–7. https://doi.org/10.1111/j.1440-1789.2008.00910.xKuru S., Sakai M., Konagaya M., Yoshida M., Hashizume Y., Saito K. An autopsy case of spinal muscular atrophy type III (Kugelberg-Welander disease). Neuropathology. 2009; 29(1): 63–7. https://doi.org/10.1111/j.1440-1789.2008.00910.x

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