Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

From diagnosis to treatment of mucopolysaccharidosis type VI: A case report with a novel variant, c.1157C>T (p.Ser386Phe), in ARSB gene

  • Yoo, Sukdong (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Lee, Jun (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Kim, Minji (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Yoon, Ju Young (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Cheon, Chong Kun (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital)
  • Received : 2021.11.23
  • Accepted : 2022.04.11
  • Published : 2022.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by the deficiency of arylsulfatase B due to mutations in the ARSB gene. Here, we report the case of a Korean female with a novel variant of MPS VI. A Korean female aged 5 years and 8 months, who is the only child of a healthy non-consanguineous Korean couple, presented at our hospital for severe short stature. She had a medical history of umbilical hernia and recurrent otitis media. Her symptoms included snoring and mouth breathing. Subtle dysmorphic features, including mild coarse face, joint contracture, hepatomegaly, and limited range of joint motion, were identified. Radiography revealed deformities, suggesting skeletal dysplasia. Growth hormone (GH) provocation tests revealed complete GH deficiency. Targeted exome sequencing revealed compound heterozygous mutations in the ARSB genes c.512G>A (p.Gly171Asp; a pathogenic variant inherited from her father) and c.1157C>T (p.Ser386Phe; a novel variant inherited from her mother in familial genetic testing). Quantitative tests revealed increased urine glycosaminoglycan (GAG) levels and decreased enzyme activity of arylsulfatase B. While on enzyme replacement therapy and GH therapy, her height increased drastically; her coarse face, joint contracture, snoring, and obstructive sleep apnea improved; urine GAG decreased; and left ventricular mass index was remarkably decreased. We report a novel variant-c.1157C>T (p.Ser386Phe)-of the ARSB gene in a patient with MPS VI; these findings will expand our knowledge of its clinical spectrum and molecular mechanisms.

Keywords

Acknowledgement

This study was supported by a 2022 research grant from Pusan National University Yangsan Hospital, Korea.

References

  1. Harmatz P, Shediac R. Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment. Front Biosci (Landmark Ed) 2017;22:385-406. https://doi.org/10.2741/4490
  2. Muenzer J. Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 2011;50 Suppl 5:v4-12. https://doi.org/10.1093/rheumatology/ker394
  3. Wichajarn K, Kim J, Yang A, Sohn YB, Lee BH, Yoo HW, et al. Clinical features, molecular analysis, and outcome of ERT in Korean patients with mucopolysaccharidosis type VI. J Korean Soc Inherit Metab Dis 2016;16:24-33.
  4. Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009;22:709-14. https://doi.org/10.1016/j.echo.2009.03.003
  5. Yang X, Wang H, Dong B, Hu B, Hao X, Chen X, et al. Standard liver volume-predicting formulae derived from normal liver volume in children under 18 years of age. Front Pediatr 2021;9:629645. https://doi.org/10.3389/fped.2021.629645
  6. Prassopoulos P, Cavouras D. CT assessment of normal splenic size in children. Acta Radiol 1994;35:152-4. https://doi.org/10.3109/02841859409172354
  7. Tomanin R, Karageorgos L, Zanetti A, Al-Sayed M, Bailey M, Miller N, et al. Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: review and classification of published variants in the ARSB gene. Hum Mutat 2018;39:1788-802. https://doi.org/10.1002/humu.23613
  8. Horovitz DDG, Leao EKEA, Ribeiro EM, Martins AM, Barth AL, Neri JICF, et al. Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: a resurvey study. Mol Genet Metab 2021;133:94-9. https://doi.org/10.1016/j.ymgme.2021.02.006
  9. Kampmann C, Lampe C, Whybra-Trumpler C, Wiethoff CM, Mengel E, Arash L, et al. Mucopolysaccharidosis VI: cardiac involvement and the impact of enzyme replacement therapy. J Inherit Metab Dis 2014;37:269-76. https://doi.org/10.1007/s10545-013-9649-4
  10. Buyukgebiz B, Eroglu Y, Kovanlikaya I, Sen A, Buyukgebiz A. Maroteaux-Lamy syndrome associated with growth hormone deficiency. J Pediatr Endocrinol Metab 1995;8:305-7. https://doi.org/10.1515/jpem.1995.8.4.305
  11. Alliston T. Chondroitin sulfate and growth factor signaling in the skeleton: possible links to MPS VI. J Pediatr Rehabil Med 2010;3:129-38. https://doi.org/10.3233/PRM-2010-0117
  12. Decker C, Yu ZF, Giugliani R, Schwartz IV, Guffon N, Teles EL, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. J Pediatr Rehabil Med 2010;3:89-100.
  13. Cattoni A, Motta S, Masera N, Gasperini S, Rovelli A, Parini R. The use of recombinant human growth hormone in patients with mucopolysaccharidoses and growth hormone deficiency: a case series. Ital J Pediatr 2019;45:93. https://doi.org/10.1186/s13052-019-0691-1
  14. Polgreen LE, Miller BS. Growth patterns and the use of growth hormone in the mucopolysaccharidoses. J Pediatr Rehabil Med 2010;3:25-38. https://doi.org/10.3233/PRM-2010-0106
  15. Quartel A, Hendriksz CJ, Parini R, Graham S, Lin P, Harmatz P. Growth charts for individuals with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). JIMD Rep 2015;18:1-11. https://doi.org/10.1007/8904_2014_333