Publication: Genotypes and phenotypes of Sri Lankan Patients with Mucopolysaccharidosis type IVA
Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Nepal Paediatric Society (JNPS)
Abstract
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.
Description
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
Keywords
Mucopolysaccharidosis type IVA, GALNS, phenotype, variant, glycosaminoglycans