Genotypes and phenotypes of Sri Lankan Patients with Mucopolysaccharidosis type IVA

Authors

  • Neluwa-Liyanage Indika Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
  • Ruwan Indika Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
  • Arndt Rolfs Arcensus GmbH, Gothestrasse 20, 18055 Rostock, Germany
  • Christian Beetz CENTOGENE GmbH, Am Strande 7, 18055 Rostock, Germany https://orcid.org/0000-0001-7061-2895
  • Sabine Schröder CENTOGENE GmbH, Am Strande 7, 18055 Rostock, Germany
  • Catarina Pereira CENTOGENE GmbH, Am Strande 7, 18055 Rostock, Germany
  • Volha Volha CENTOGENE GmbH, Am Strande 7, 18055 Rostock, Germany
  • Mihika Fernando Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka https://orcid.org/0000-0001-8322-5704
  • Dinesha Maduri Vidanapathirana Department of Pathology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka https://orcid.org/0000-0003-2698-088X
  • Subhashinie Jayasena Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka
  • Eresha Jasinge Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka https://orcid.org/0000-0001-6265-0461

DOI:

https://doi.org/10.3126/jnps.v42i2.41954

Keywords:

Mucopolysaccharidosis type IVA, GALNS, phenotype, variant, glycosaminoglycans

Abstract

Mucopolysaccharidosis type IVA is a rare autosomal recessive lysosomal storage disorder occurring worldwide in all ethnic groups. It is caused by biallelic variants in the GALNS gene (OMIM 612222). We report five cases of mucopolysaccharidosis type IVA with short stature and severe skeletal dysplasia. An optimized diagnostic strategy that combined enzymatic testing and genetic screening was applied. All the tested urine samples showed increased urinary glycosaminoglycan / creatinine ratios. In all five cases, the enzyme activity of galactosamine-6-sulfate sulfatase was pathologically decreased. Gene-targeted sequencing revealed a previously unreported homozygous c.139-12T>C variant of the GALNS gene in one patient and three previously reported missense variants in four patients; c.253T>C (p.Cys85Arg), c.626C>T (p.Ala209Val) and c.878C>T (p.Ser293Leu). Genetic studies not only confirm the diagnosis of mucopolysaccharidosis IVA, but also enable predicting the prognosis and facilitate genetic counseling. Enzyme replacement therapy is not available in Sri Lanka to date. However, the quality of life in these patients can be improved by a multidisciplinary approach.

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Published

2022-12-31

How to Cite

Indika, N.-L., Indika, R., Rolfs, A., Beetz, C., Schröder, S., Pereira, C., Volha, V., Fernando, M., Vidanapathirana, D. M., Jayasena, S., & Jasinge, E. (2022). Genotypes and phenotypes of Sri Lankan Patients with Mucopolysaccharidosis type IVA. Journal of Nepal Paediatric Society, 42(2), 80–82. https://doi.org/10.3126/jnps.v42i2.41954

Issue

Vol. 42 No. 2 (2022)

Section

Case Series

License

Copyright (c) 2022 Neluwa-Liyanage Indika, Ruwan Indika, Arndt Rolfs, Christian Beetz, Sabine Schröder, Catarina Pereira, Volha Volha, Mihika Fernando, Dinesha Maduri Vidanapathirana, Subhashinie Jayasena, Eresha Jasinge

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