Mucopolysaccharidosis type IVA in children: Clinical cases

Background. Mucopolysaccharidosis type IVA (Morquio syndrome) is a rare genetic lysosomal storage disease. Due to rarity, the syndrome is typically diagnosed at a later stage of gross affections of musculoskeletal and central nervous systems, leading to disability and a markedly reduced quality of life. A replacement therapy is nowadays available with recombinant human N-acetylgalactosamine-6-sulfatase (elosulfase alfa) enzyme.

Clinical cases description. Two siblings, 10-yo male and 8-yo female, were admitted with complaints of growth retardation, deformity of the spine, thorax and joints, impaired hearing and visual acuity, poor tolerance to exercise. In the boy’s medical history, first manifestations appeared in the first year of life and progressed gradually; the patient was being observed as spondylodysplastic. Mental development was unaffected. The diagnosis was confirmed only by age of 7 at the National Medical Research Center for Children's Health Federal State Autonomous Institution of the Ministry of Health of the Russian Federation. Genotyping revealed two SNP mutations in gene GALNS (g.88909227C>A and g.88884454G>A in heterozygous state), and enzymatic assays — a severely reduced N-acetylgalactosamin-6-sulfatase activity. A routine elosulfase alfa replacement therapy has been received since 8-year age.

The younger sister had neonatal cardiomegaly; congenital carditis and cardiomyopathy not excluded. Musculoskeletal affections developed by age of 3–4 years. By age of 5 and simultaneously with brother, the same GALNS mutations and severely impaired N-acetylgalactosamine-6-sulfatase activity were detected. A replacement therapy has been routinely received since 6-year age. The therapy triggered positive dynamics of restoring activity and muscle strength in both children, as well as significantly abating the musculoskeletal affection progress.

Conclusion. The clinical cases of Morquio syndrome presented demonstrate its long-term and complex diagnosis. A replacement therapy is nowadays available, which warrants an earliest disease detection to halt progression and improve the patient’s life quality and expectancy.

1. Ge Z., Mao J., Shen H., Xu Y., Fu H., Zhang W., Li D. Clinical and genetic characteristics of concomitant Mucopolysaccharidosis type IVA and neurogenic bladder in children: two case reports and literature review. BMC Pediatr. 2021; 21(1): 18. DOI: 10.1186/s12887-020-02484-0

2. Morrone A., Caciotti A., Atwood R., Davidson K., Du C., Francis-Lyon P., Harmatz P., Mealiffe M., Mooney S., Oron T.R., Ryles A., Zawadzki K.A., Miller N. Morquio A syndrome-associated mutations: a review of alterations in the GALNS gene and a new locus-specific database. Hum. Mutat. 2014; 35(11): 1271–1279. DOI: 10.1002/humu.22635

3. Polyakova O.A., Mikhailova L.K., Sadovskaya Y.E., Tyrtseva E.S., Suyundukova A.S. Difficulties in the diagnosis of mucopolysaccharidosis in children. Kremlin Medicine Journal. 2019; 4: 57–66 (In Russ., English abstract). DOI: 10.26269/jfme-5t33

4. Osipova L.A., Kuzenkova L.M., Namazova-Baranova L.S., Gevorkyan A.K., Podkletnova T.V., Vashakmadze N.D. Neuronopathic Types of Mucopolysaccharidoses: Pathogenesis and Emerging Treatments. Current Pediatrics. 2015; 14(5): 539–547 (In Russ., English abstract). DOI: 10.15690/vsp.v14i5.1436

5. Suarez-Guerrero J.L., Gómez Higuera P.J., Arias Flórez J.S., Contreras-García G.A. Mucopolisacaridosis: características clínicas, diagnóstico y de manejo [Mucopolysaccharidosis: clinical features, diagnosis and management]. Rev. Chil. Pediatr. 2016; 87(4): 295–304. Spanish. DOI: 10.1016/j.rchipe.2015.10.004

6. Khan S., Alméciga-Díaz C.J., Sawamoto K., Mackenzie W.G., Theroux M.C., Pizarro C., Mason R.W., Orii T., Tomatsu S. Mucopolysaccharidosis IVA and glycosaminoglycans. Mol. Genet. Metab. 2017; 120(1–2): 78–95. DOI: 10.1016/j.ymgme.2016.11.007

7. Sawamoto K., Álvarez González J.V., Piechnik M., Otero F.J., Couce M.L., Suzuki Y., Tomatsu S. Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int. J. Mol. Sci. 2020; 21(4): 1517. DOI: 10.3390/ijms21041517

8. Khan S.A., Peracha H., Ballhausen D., Wiesbauer A., Rohrbach M., Gautschi M., Mason R.W., Giugliani R., Suzuki Y., Orii K.E., Orii T., Tomatsu S. Epidemiology of mucopolysaccharidoses. Mol. Genet. Metab. 2017; 121(3): 227–240. DOI: 10.1016/j.ymgme.2017.05.016

9. Kenis V.M., Melchenko E.V., Markova T.V., Al Kaissi A., Sapogovskiy A.V., Agranovich O.V., Petrova E.V. Upper Limb Pathology in Children with Mucopolysaccharidoses. Traumatology and Orthopedics of Russia. 2021; 27(2): 34–43 (In Russ., English abstract). DOI: 10.21823/2311-2905-2021-27-2-34-43

10. Peracha H., Sawamoto K., Averill L., Kecskemethy H., Theroux M., Thacker M., Nagao K., Pizarro C., Mackenzie W., Kobayashi H., Yamaguchi S., Suzuki Y., Orii K., Orii T., Fukao T., Tomatsu S. Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA. Mol. Genet. Metab. 2018; 125(1–2): 18–37. DOI: 10.1016/j.ymgme.2018.05.004

11. Buchinskaya N.V., Chikova I.А., Isupova E.А., Kalashnikova О.V., Kostik М.М., Chasnyk V.G. Modern approaches to therapy for children with mucopolysaccharidosis. Current Pediatrics. 2014; 13(3): 35-43 (In Russ., English abstract). DOI: 10.15690/vsp.v13i3.1026

12. Regier D.S., Tanpaiboon P. Role of elosulfase alfa in mucopolysaccharidosis IVA. Appl. Clin. Genet. 2016; 9: 67–74. DOI: 10.2147/TACG.S69080

13. Long B., Tompkins T., Decker C., Jesaitis L., Khan S., Slasor P., Harmatz P., O’Neill C.A., Schweighardt B. Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study. Clin. Ther. 2017; 39(1): 118–129.e3. DOI: 10.1016/j.clinthera.2016.11.017

14. Do Cao J., Wiedemann A., Quinaux T., Battaglia-Hsu S.F., Mainard L., Froissart R., Bonnemains C., Ragot S., Leheup B., Journeau P., Feillet F. 30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case. Mol. Genet. Metab. Rep. 2016; 9: 42–45. DOI: 10.1016/j.ymgmr.2016.10.001

15. White K.K., Jester A., Bache C.E., Harmatz P.R., Shediac R., Thacker M.M., Mackenzie W.G. Orthopedic management of the extremities in patients with Morquio A syndrome. J. Child Orthop. 2014; 8(4): 295–304. DOI: 10.1007/s11832-014-0601-4