Case report: A Thai patient with mucopolysaccharidosis type IVA (Morquio syndrome type A) - clinical phenotypes and GALNS gene mutation analysis
Keywords:
Mucopolysaccharidosis type IVA, Morquio syndrome type A, GALNS geneAbstract
Background : Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome type A is an autosomal recessive disorder. N-acetylgalactosamine-sulfate sulfatase (GALNS) gene is the disease-causing gene of MPS IVA. Objective : The aim of our study is to study clinical phenotypes, skeletal findings, and molecular analysis in one Thai patient with the severe type of MPS IVA.
Methods : We reviewed the clinical features and family history of the patient. We performed GALNS and B-galactosidase enzyme assay in her blood leukocytes. The GALNS gene mutation analysis was performed on gDNA derived from blood leukocytes of the patient and her parents.
Results : A 3 3/12-year-old Thai girl has presented with abnormal gait and disproportionate short stature for 18 months. Skeletal survey revealed unique skeletal dysplasia known as dysostosis multiplex. GALNS enzyme assay showed low enzyme activity with normal B-galactosidase level. Direct sequencing analysis of the GALNS gene identified the compound heterozygous mutations, c.463G>A (p.G155R) and c.1175C>T (p.A392V). These two missense mutations have been previously reported in patients with MPS IVA.
Conclusion : MPS IVA should be suspected in an individual with disproportionate short stature and genu valgum. Since the GALNS gene has a marked molecular heterogeneity, we need to do the molecular study in the larger number of Thai patients with MPS IVA on a national scale to elucidate the clinical phenotypes and mutational spectrum in Thai patients
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References
Sawamoto K, Alvarez Gonzalez JV, Piechnik M, et al. Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int J Mol Sci. 2020;21(4).
Morquio L. Sur une fome de dystrophie osseuse familiale. Bull Soc Pediatr Paris. 1929;27:145-52.
Brailsford J. Chondro-osteo-dystrophy, roentgenopgraphic & clinical features of a child with dislocation of vertebrae. Am J Surg. 1929;7:404-10.
Chudley AE, Chakravorty C. Genetic landmarks through philately: Luis Morquio1867-1935. Clin Genet. 2002;62:438-9.
Holzgreve W, Grobe H, von Figura K, Kresse H, Beck H, Mattei JF. Morquio syndrome: clinical findings in 11 patients with MPS IVA and 2 patients with MPS IVB. Hum Genet. 1981;57:360-5.
Northover H, Cowie RA, Wraith JE. Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. J Inherit Metab Dis. 1996;19:357-65.
Dhawale AA, Thacker MM, Belthur MV, Rogers K, Bober MB, Mackenzie WG. The lower extremity in Morquio syndrome. J Pediatr Orthop. 2012;32:534-40.
E g g l i K D , D o r s t J P. T h e mucopolysaccharidoses and related conditions. Semin Roentgenol. 1986;21: 275-94.
Hendriksz CJ, Harmatz P, Beck M, et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013;110:54-64.
Tomatsu S, Fukuda S, Masue M, et al. Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase. Biochem Biophys Res Commun. 1991;181:677-83.
Nakashima Y, Tomatsu S, Hori T, et al. Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine- 6-sulfatase gene (GALNS) and analysis of the 5’-flanking region. Genomics. 1994;20:99-104.
Jezela-Stanek A, Rozdzynska-Swiatkowska A, Kulpanovich A, Ciara E, Marucha J, Tylki-Szymanska A. Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe. J Appl Genet. 2019;60:163-74.
van Diggelen OP, Zhao H, Kleijer WJ, et al. A fluorimetric enzyme assay for the diagnosis of Morquio disease type A (MPS IV A). Clin Chim Acta. 1990;187:131-9.
Baratela WA, Bober MB, Thacker MM, et al. Cervicothoracic myelopathy in children with Morquio syndrome A: a report of 4 cases. J Pediatr Orthop. 2014;34:223-8.
Montano AM, Tomatsu S, Gottesman GS, Smith M, Orii T. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007;30:165-74.
Regier DS, Oetgen M, Tanpiboon P. Mucopolysaccharidosis Type IVA. GeneReviews University of Wahsington: Seattle, WA, USA; 2016 [updated March 24,2016. Available from: https://www.ncbi.nlm.nih.gov/books/NBK148668/.
Tomatsu S, Montano AM, Nishioka T, et al. Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A). Hum Mutat. 2005;26(6):500-12.
He D, Huang Y, Ou Z, et al. Molecular genetic assay of mucopolysaccharidosis IVA in South China. Gene. 2013;532(1):46-52.
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