Clinical and Molecular Characterization of Mucopolysaccharidosis Type 3A and 3B in a Turkish Series

Overview

Journal Mol Syndromol

Date 2024 Jun 6

PMID 38841321

Authors

Bilge Noyan

Nursel H Elcioglu

Abdellah Tebani

Soumeya Bekri

Affiliations

Soon will be listed here.

Abstract

Introduction: Sanfilippo syndrome or mucopolysaccharidosis type 3 (MPS-3) is a rare condition and its epidemiological data are still not defined. MPS-3 is linked to a deficiency in enzymes involved in heparan sulfate degradation. This biomolecule is neurotoxic and its accumulation underlies the severe central nervous system degeneration observed in this disease.

Methods: Here, we describe 15 Turkish patients with MPS-3A or MPS-3B subtypes. Clinical data upon the diagnosis and during the follow-up as well as molecular characterization are reported.

Results: Two and ten distinct variants were identified in and gene sequences, respectively. Six variants ( NM_000263.3:c.532-?_c.764+?del, NAGLU NM_000263.3: c.509G>T, NM_000263.3: c.700C>G, NM_000263.3:c.507_516 del, NM dises_000263.3: c.1354 G>A, NM_000263.3: c.200T>C) have been previously published and 6 are novel ( NM_000199.4: c.80T>G, NM_000199.4: c.7_16del, NM_000263.3: c.224_235del, NM_000263.3: c.904G>T, NM_000263.3: c.626C>T, NM_000263.3: c.1241A>G). NM_000199.4:c.7_16del variation might be caused by a founder effect.

Conclusion: Due to the high rate of consanguinity in Turkey, the incidence of Sanfilippo syndrome might be higher compared to other populations worldwide. Our results contribute to the characterization of rare diseases in Turkey and to improve our knowledge of the clinical, molecular, and epidemiological aspects of MPS-3 disease.

References

Shapiro E, King K, Ahmed A, Rudser K, Rumsey R, Yund B . The Neurobehavioral Phenotype in Mucopolysaccharidosis Type IIIB: an Exploratory Study. Mol Genet Metab Rep. 2016; 6:41-47. PMC: 4762067. DOI: 10.1016/j.ymgmr.2016.01.003. View

Sudrie-Arnaud B, Marguet F, Patrier S, Martinovic J, Louillet F, Broux F . Metabolic causes of nonimmune hydrops fetalis: A next-generation sequencing panel as a first-line investigation. Clin Chim Acta. 2018; 481:1-8. DOI: 10.1016/j.cca.2018.02.023. View

Wijburg F, Whitley C, Muenzer J, Gasperini S, Del Toro M, Muschol N . A multicenter open-label extension study of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A. Mol Genet Metab. 2021; 134(1-2):175-181. DOI: 10.1016/j.ymgme.2021.07.001. View

Emre S, Terzioglu M, Tokatli A, Coskun T, Ozalp I, Weber B . Sanfilippo syndrome in Turkey: Identification of novel mutations in subtypes A and B. Hum Mutat. 2002; 19(2):184-5. DOI: 10.1002/humu.9009. View

Shapiro E, Eisengart J . The natural history of neurocognition in MPS disorders: A review. Mol Genet Metab. 2021; 133(1):8-34. DOI: 10.1016/j.ymgme.2021.03.002. View

Beesley C, Young E, Vellodi A, Winchester B . Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB). J Med Genet. 1998; 35(11):910-4. PMC: 1051483. DOI: 10.1136/jmg.35.11.910. View

Sudrie-Arnaud B, Snanoudj S, Dabaj I, Dranguet H, Abily-Donval L, Lebas A . Next-Generation Molecular Investigations in Lysosomal Diseases: Clinical Integration of a Comprehensive Targeted Panel. Diagnostics (Basel). 2021; 11(2). PMC: 7918778. DOI: 10.3390/diagnostics11020294. View

Yilmaz B, Davison J, Jones S, Baruteau J . Novel therapies for mucopolysaccharidosis type III. J Inherit Metab Dis. 2020; 44(1):129-147. PMC: 8436764. DOI: 10.1002/jimd.12316. View

Bunge S, Knigge A, Steglich C, Kleijer W, van Diggelen O, Beck M . Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha-N-acetylglucosaminidase gene mutations. J Med Genet. 1999; 36(1):28-31. PMC: 1762943. View

10.

Valstar M, Bruggenwirth H, Olmer R, Wevers R, Verheijen F, Poorthuis B . Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype. J Inherit Metab Dis. 2010; 33(6):759-67. PMC: 2992652. DOI: 10.1007/s10545-010-9199-y. View

11.

Heron B, Mikaeloff Y, Froissart R, Caridade G, Maire I, Caillaud C . Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med Genet A. 2011; 155A(1):58-68. DOI: 10.1002/ajmg.a.33779. View

12.

Valstar M, Ruijter G, van Diggelen O, Poorthuis B, Wijburg F . Sanfilippo syndrome: a mini-review. J Inherit Metab Dis. 2008; 31(2):240-52. DOI: 10.1007/s10545-008-0838-5. View

13.

Meikle P, Hopwood J, Clague A, Carey W . Prevalence of lysosomal storage disorders. JAMA. 1999; 281(3):249-54. DOI: 10.1001/jama.281.3.249. View

14.

Valstar M, Neijs S, Bruggenwirth H, Olmer R, Ruijter G, Wevers R . Mucopolysaccharidosis type IIIA: clinical spectrum and genotype-phenotype correlations. Ann Neurol. 2010; 68(6):876-87. DOI: 10.1002/ana.22092. View

15.

Ozkinay F, Emecen D, Kose M, Isik E, Bozaci A, Canda E . Clinical and genetic features of 13 patients with mucopolysaccarhidosis type IIIB: Description of two novel gene mutations. Mol Genet Metab Rep. 2021; 27:100732. PMC: 7966861. DOI: 10.1016/j.ymgmr.2021.100732. View

16.

Kim Y, Park H, Jang M, Ki C, Lee S, Kim J . A novel mutation (c.200T>C) in the NAGLU gene of a Korean patient with mucopolysaccharidosis IIIB. Ann Lab Med. 2013; 33(3):221-4. PMC: 3646201. DOI: 10.3343/alm.2013.33.3.221. View

17.

Deiva K, Ausseil J, de Bournonville S, Zerah M, Husson B, Gougeon M . Intracerebral Gene Therapy in Four Children with Sanfilippo B Syndrome: 5.5-Year Follow-Up Results. Hum Gene Ther. 2021; 32(19-20):1251-1259. DOI: 10.1089/hum.2021.135. View

18.

Saville J, Derrick-Roberts A, McIntyre C, Fuller M . Systemic scAAV9.U1a.hSGSH Delivery Corrects Brain Biochemistry in Mucopolysaccharidosis Type IIIA at Early and Later Stages of Disease. Hum Gene Ther. 2020; 32(7-8):420-430. DOI: 10.1089/hum.2020.253. View

19.

Andrade F, Aldamiz-Echevarria L, Llarena M, Couce M . Sanfilippo syndrome: Overall review. Pediatr Int. 2015; 57(3):331-8. DOI: 10.1111/ped.12636. View