vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v21i6S.2499vsp-3080Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWКлиническая характеристика пациента с мукополисахаридозом, тип IVА (синдромом Моркио)Clinical Characteristics of a Patient with Mucopolysaccharidosis Type IVA (Morquio Syndrome)https://orcid.org/0000-0001-8320-2027ВашакмадзеН. Д.VashakmadzeNato D.

Вашакмадзе Нато Джумберовна - доктор медицинских наук, заведующая отделом орфанных болезней и профилактики инвалидизирующих заболеваний НИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ «РНЦХ им. акад. Б.В. Петровского» Минобрнауки России.

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nato-nato@yandex.ruhttps://orcid.org/0000-0001-6614-6115ЖурковаН. В.ZhurkovaNatalia V.

Москва

Moscow

https://orcid.org/0000-0002-3346-865XМихайловаЛ. К.MikhaylovaLudmila K.

Москва

Moscow

https://orcid.org/0000-0002-3720-8046СмирноваО. Я.SmirnovaVolha Ya.

Москва

Moscow

https://orcid.org/0000-0001-7834-213XРевуненковГ. В.RevunenkovGrigorii V.

Москва

Moscow

НИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ РНЦХ им. акад. Б.В. Петровского; РНИМУ им. Н.И. ПироговаРоссияResearch Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical UniversityRussian FederationНИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ РНЦХ им. акад. Б.В. Петровского; МГНЦ им. Н.П. БочковаРоссияResearch Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Research Centre for Medical GeneticsRussian FederationНИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ РНЦХ им. акад. Б.В. ПетровскогоРоссияResearch Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of SurgeryRussian Federation202220012023216S529534Copyright © Вашакмадзе Н.Д., Журкова Н.В., Михайлова Л.К., Смирнова О.Я., Ревуненков Г.В., 20232023Вашакмадзе Н.Д., Журкова Н.В., Михайлова Л.К., Смирнова О.Я., Ревуненков Г.В.Vashakmadze N.D., Zhurkova N.V., Mikhaylova L.K., Smirnova V.Y., Revunenkov G.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/3080

Мукополисахаридоз (МПС), тип IVА (синдром Моркио) — наследственная лизосомная болезнь накопления, вызванная дефицитом N-ацетилглюкозамин-6-сульфатной сульфатазы. Дефицит этого фермента приводит к накоплению специфических гликозаминогликанов — кератансульфата и хондроитин-6-сульфата — преимущественно в костной и хрящевой ткани, а также в сердечно-сосудистой и дыхательной системах, зрительном анализаторе. При рождении пациенты с MПС IVА выглядят здоровыми, однако уже с первых лет жизни появляются характерные деформации позвоночника (кифосколиоз), килевидная грудная клетка, разболтанность запястий со снижением мышечной силы и утратой мелкой моторики, вальгусная деформация нижних конечностей. Обнаруживаются патологические изменения кардиоваскулярной и дыхательной систем, зрительного и слухового анализаторов. Ранняя диагностика заболевания необходима для своевременного начала ферментной заместительной терапии. Однако редкость заболевания и гетерогенная клиническая картина затрудняют своевременную верификацию диагноза. В результате пациенты c МПС IVА часто становятся тяжелыми инвалидами уже в подростковом возрасте. Больные с тяжелой формой при отсутствии лечения умирают в возрасте до 30 лет от осложнений болезней дыхательной системы и/или поражения клапанного аппарата сердца и шейной миелопатии.

Mucopolysaccharidosis (MPS) type IVA (Morquio syndrome) is a hereditary lysosomal storage disease caused by deficiency of N-acetylglucosamine-6-sulfate sulfatase. This enzyme deficiency leads to specific glycosaminoglycans (keratan sulfate and chondroitin-6sulfate) accumulation mainly in the bone and cartilage tissues, as well as in the cardiovascular, respiratory systems, and visual systems. Patients with MPS IVA look healthy at birth, however, they develop typical spine deformities (kyphoscoliosis), pectus carinatum, wrists hypermobility with decreased muscle strength and loss of fine motor skills, valgus deformation of lower limbs during the first years of life. Pathological changes in cardiovascular and respiratory systems, visual and acoustic analyzers can be revealed. Early diagnosis of the disease is crucial for timely initiation of enzyme replacement therapy. Thus, low incidence of the disease and its heterogeneous clinical picture complicates diagnosis. Consequently, patients with MAS IVA often become severely disabled as early as adolescence. Patients with severe form and without treatment die before the age of 30 due to complications of respiratory system diseases, valvular heart apparatus involvement, and cervical myelopathy.

мукополисахаридоз IVА типасиндром Моркиоферментозаместительная терапиялизосомная болезнь накоплениягликозаминогликаныкератансульфатN-ацетилглюкозамин-6-сульфатная сульфатазапомутнение роговицыкороткая шеяmucopolysaccharidosis type IVAMorquio syndromeenzyme replacement therapylysosomal storage diseaseglycosaminoglycanskeratan sulfateN-acetylglucosamine-6-sulfate sulfatasecorneal opacityshort neckИсточник финансирования отсутствуетNot specifiedReferencesNakashima Y, Tomatsu S, Hori T, et al. Mucopolysaccharidosis IV A: Molecular cloning of the human N-acetylgalactosamine-6sulfatase gene (GALNS) and analysis of the 5-flanking region. Genomics. 1994;20(1):99–104. doi: https://doi.org/10.1006/geno.1994.1132Nakashima Y, Tomatsu S, Hori T, et al. Mucopolysaccharidosis IV A: Molecular cloning of the human N-acetylgalactosamine-6sulfatase gene (GALNS) and analysis of the 5-flanking region. Genomics. 1994;20(1):99–104. doi: https://doi.org/10.1006/geno.1994.1132Jezela-Stanek A, Różdżyńska-Świątkowska A, Kulpanovich A, et al. Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe. J Appl Genet. 2019;60(2):163–174. doi: https://doi.org/10.1007/s13353-019-00491-1Jezela-Stanek A, Różdżyńska-Świątkowska A, Kulpanovich A, et al. Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe. J Appl Genet. 2019;60(2):163–174. doi: https://doi.org/10.1007/s13353-019-00491-1Hendriksz CJ, Harmatz P, Beck M, et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013;110(1-2):54–64. doi: https://doi.org/10.1016/j.ymgme.2013.04.002Hendriksz CJ, Harmatz P, Beck M, et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013;110(1-2):54–64. doi: https://doi.org/10.1016/j.ymgme.2013.04.002Hendriksz CJ, Berger KI, Giugliani R, et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015;167A(1):11–25. doi: https://doi.org/10.1002/ajmg.a.36833Hendriksz CJ, Berger KI, Giugliani R, et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015;167A(1):11–25. doi: https://doi.org/10.1002/ajmg.a.36833Khan S, Alméciga-Díaz CJ, Sawamoto K, et al. Mucopolysaccharidosis IVA and glycosaminoglycans. Mol Genet Metab. 2017;120(1-2): 78–95. doi: https://doi.org/10.1016/j.ymgme.2016.11.007Khan S, Alméciga-Díaz CJ, Sawamoto K, et al. Mucopolysaccharidosis IVA and glycosaminoglycans. Mol Genet Metab. 2017;120(1-2): 78–95. doi: https://doi.org/10.1016/j.ymgme.2016.11.007Sawamoto K, Alméciga-Díaz CJ, Mason RW, et al. Mucopolysaccharidosis type IVA: Clinical features, biochemistry, diagnosis, genetics, and treatment. In: Mucopolysaccharidoses Update. Tomatsu S, Lavery C, Giugliani R, eds. New York, NY: Nova Science Publishers; 2018. pp. 235–272.Sawamoto K, Alméciga-Díaz CJ, Mason RW, et al. Mucopolysaccharidosis type IVA: Clinical features, biochemistry, diagnosis, genetics, and treatment. In: Mucopolysaccharidoses Update. Tomatsu S, Lavery C, Giugliani R, eds. New York, NY: Nova Science Publishers; 2018. pp. 235–272.Brailsford JF. Chondro-osteo-dystrophy, roentgenopgraphic & clinical features of a child with dislocation of vertebrae. Am J Surg. 1929;7:404–410.Brailsford JF. Chondro-osteo-dystrophy, roentgenopgraphic & clinical features of a child with dislocation of vertebrae. Am J Surg. 1929;7:404–410.Morquio L. Sur une forme de dystrophie osseuse familial. Arch Med Enfants Paris. 1929;32:129–135.Morquio L. Sur une forme de dystrophie osseuse familial. Arch Med Enfants Paris. 1929;32:129–135.Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Hum Genet. 2003;123A(3): 310–313. doi: https://doi.org/10.1002/ajmg.a.20314Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Hum Genet. 2003;123A(3): 310–313. doi: https://doi.org/10.1002/ajmg.a.20314Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet. 1997;101(3):355–358. doi: https://doi.org/10.1007/s004390050641Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet. 1997;101(3):355–358. doi: https://doi.org/10.1007/s004390050641Sawamoto K, González J, Piechnik M, et al. Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int J Mol Sci. 2020;21(4):1517. doi: https://doi.org/10.3390/ijms21041517Sawamoto K, González J, Piechnik M, et al. Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int J Mol Sci. 2020;21(4):1517. doi: https://doi.org/10.3390/ijms21041517Morrone A, Caciotti A, Atwood R, et al. Morquio A syndromeassociated mutations: A review of alterations in the GALNS gene and a new locus-specific database. Hum Mutat. 2014;35(11): 1271–1279. doi: https://doi.org/10.1002/humu.22635Morrone A, Caciotti A, Atwood R, et al. Morquio A syndromeassociated mutations: A review of alterations in the GALNS gene and a new locus-specific database. Hum Mutat. 2014;35(11): 1271–1279. doi: https://doi.org/10.1002/humu.22635Peracha H, Sawamoto K, Averill L, et al. Diagnosis and prognosis of Mucopolysaccharidosis IVA. Mol Genet Metab. 2018;125 (1-2):18–37. doi: https://doi.org/10.1016/j.ymgme.2018.05.004Peracha H, Sawamoto K, Averill L, et al. Diagnosis and prognosis of Mucopolysaccharidosis IVA. Mol Genet Metab. 2018;125 (1-2):18–37. doi: https://doi.org/10.1016/j.ymgme.2018.05.004Doherty C, Stapleton M, Piechnik M, et al. Effect of enzyme replacement therapy on the growth of patients with Morquio A. J Hum Genet. 2019;64(7):625–635. doi: https://doi.org/10.1038/s10038-019-0604-6Doherty C, Stapleton M, Piechnik M, et al. Effect of enzyme replacement therapy on the growth of patients with Morquio A. J Hum Genet. 2019;64(7):625–635. doi: https://doi.org/10.1038/s10038-019-0604-6Do Cao J, Wiedemann A, Quinaux T, et al. 30 months followup of an early enzyme replacement therapy in a severe Morquio A patient: About one case. Mol Genet Metab Rep. 2016;9:42–45. doi: https://doi.org/10.1016/j.ymgmr.2016.10.001Do Cao J, Wiedemann A, Quinaux T, et al. 30 months followup of an early enzyme replacement therapy in a severe Morquio A patient: About one case. Mol Genet Metab Rep. 2016;9:42–45. doi: https://doi.org/10.1016/j.ymgmr.2016.10.001Dhawale AA, Thacker MM, Belthur MV, et al. The Lower Extremity in Morquio Syndrome. J Pediatr Orthop. 2012;32(5):534–540. doi: https://doi.org/10.1097/BPO.0b013e318259fe57Dhawale AA, Thacker MM, Belthur MV, et al. The Lower Extremity in Morquio Syndrome. J Pediatr Orthop. 2012;32(5):534–540. doi: https://doi.org/10.1097/BPO.0b013e318259fe57Tomatsu S, Yasuda E, Patel P, et al. Morquio A syndrome: Diagnosis and current and future therapies. Pediatr Endocrinol Rev. 2014; 12 Suppl 1(0-1):141–151.Tomatsu S, Yasuda E, Patel P, et al. Morquio A syndrome: Diagnosis and current and future therapies. Pediatr Endocrinol Rev. 2014; 12 Suppl 1(0-1):141–151.White KK, Jester A, Bache CE, et al. Orthopedic management of the extremities in patients with Morquio A syndrome. J Child Orthop. 2014;8(4):295–304. doi: https://doi.org/10.1007/s11832-014-0601-4White KK, Jester A, Bache CE, et al. Orthopedic management of the extremities in patients with Morquio A syndrome. J Child Orthop. 2014;8(4):295–304. doi: https://doi.org/10.1007/s11832-014-0601-4Tomatsu S, Averill LW, Sawamoto K, et al. Obstructive airway in Morquio A syndrome, the past, the present and the future. Mol Genet Metab. 2016;117(2):150–156. doi: https://doi.org/10.1016/j.ymgme.2015.09.007Tomatsu S, Averill LW, Sawamoto K, et al. Obstructive airway in Morquio A syndrome, the past, the present and the future. Mol Genet Metab. 2016;117(2):150–156. doi: https://doi.org/10.1016/j.ymgme.2015.09.007Lavery C, Hendriksz C. Mortality in Patients with Morquio Syndrome A. JIMD Rep. 2015;15:59–66. doi: https://doi.org/10.1007/8904_2014_298Lavery C, Hendriksz C. Mortality in Patients with Morquio Syndrome A. JIMD Rep. 2015;15:59–66. doi: https://doi.org/10.1007/8904_2014_298Pizarro C, Davies RR, Theroux M, et al. Surgical Reconstruction for Severe Tracheal Obstruction in Morquio A Syndrome. Ann Thorac Surg. 2016;102(4):e329–e331. doi: https://doi.org/10.1016/j.athoracsur.2016.02.113Pizarro C, Davies RR, Theroux M, et al. Surgical Reconstruction for Severe Tracheal Obstruction in Morquio A Syndrome. Ann Thorac Surg. 2016;102(4):e329–e331. doi: https://doi.org/10.1016/j.athoracsur.2016.02.113Sumner J, Tomatsu S, Stapleton M, et al. Management of tracheal obstruction in MPS. In: Mucopolysaccharidoses Update. Tomatsu S, Lavery C, Giugliani R, eds. New York, NY: Nova Science Publishers; 2018. pp. 689–710,Sumner J, Tomatsu S, Stapleton M, et al. Management of tracheal obstruction in MPS. In: Mucopolysaccharidoses Update. Tomatsu S, Lavery C, Giugliani R, eds. New York, NY: Nova Science Publishers; 2018. pp. 689–710,Harmatz PR, Mengel E, Geberhiwot T, et al. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study. Am J Med Genet A. 2017;173(2):375–383. doi: https://doi.org/10.1002/ajmg.a.38014Harmatz PR, Mengel E, Geberhiwot T, et al. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study. Am J Med Genet A. 2017;173(2):375–383. doi: https://doi.org/10.1002/ajmg.a.38014Leone A, Rigante D, Amato DZ, et al. Spinal involvement in mucopolysaccharidoses: a review. Childs Nerv Syst. 2015;31(2): 203–212. doi: https://doi.org/10.1007/s00381-014-2578-1Leone A, Rigante D, Amato DZ, et al. Spinal involvement in mucopolysaccharidoses: a review. Childs Nerv Syst. 2015;31(2): 203–212. doi: https://doi.org/10.1007/s00381-014-2578-1Nicolini F, Corradi D, Bosio S, Gherli T. Aortic valve replacement in a patient with Morquio syndrome. Heart Surg Forum. 2008;11(2): E96–E98. doi: https://doi.org/10.1532/HSF98.20071197Nicolini F, Corradi D, Bosio S, Gherli T. Aortic valve replacement in a patient with Morquio syndrome. Heart Surg Forum. 2008;11(2): E96–E98. doi: https://doi.org/10.1532/HSF98.20071197Braunlin EA, Harmatz PR, Scarpa M, et al. Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis. 2011;34(6):1183–1197. doi: https://doi.org/10.1007/s10545-011-9359-8Braunlin EA, Harmatz PR, Scarpa M, et al. Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis. 2011;34(6):1183–1197. doi: https://doi.org/10.1007/s10545-011-9359-8John RM, Hunter D, Swanton RH. Echocardiographic abnormalities in type IV mucopolysaccharidosis. Arch Dis Child. 1990; 65(70):746–749. doi: https://doi.org/10.1136/adc.65.7.746John RM, Hunter D, Swanton RH. Echocardiographic abnormalities in type IV mucopolysaccharidosis. Arch Dis Child. 1990; 65(70):746–749. doi: https://doi.org/10.1136/adc.65.7.746Lin HY, Chuang CK, Ke YY, et al. Long-term effects of enzyme replacement therapy for Taiwanese patients with mucopolysaccharidosis IVA. Pediatr Neonatol. 2019;60(3):342–343. doi: https://doi.org/10.1016/j.pedneo.2018.08.005Lin HY, Chuang CK, Ke YY, et al. Long-term effects of enzyme replacement therapy for Taiwanese patients with mucopolysaccharidosis IVA. Pediatr Neonatol. 2019;60(3):342–343. doi: https://doi.org/10.1016/j.pedneo.2018.08.005

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