Araştırma Makalesi

GM2 gangliosidoses: evaluation of clinical, biochemical and genetic findings of patients with three novel mutations

Cilt: 46 Sayı: 3 30 Eylül 2021
Berrak Bilginer Gürbüz *, Fatma Derya Bulut , Habibe Koç Uçar , Esra Sarıgeçili , Bilge Sarıkepe , Özge Özalp Yüreğir
PDF İndir
Cukurova Medical Journal Kapak Cukurova Medical Journal
EN TR

GM2 gangliosidoses: evaluation of clinical, biochemical and genetic findings of patients with three novel mutations

Abstract

Purpose: The aim of this study is to evaluate the diagnosis characteristics, clinic findings, phenotypical and genotypical features of children with GM2 gangliosidoses. Materials and Methods: The file records of 14 patients diagnosed with GM2 gangliosidoses in our clinic were retrospectively reviewed. The GM2 gangliosidoses diagnosis was confirmed by determining the levels of serum total hexosaminidase and β-hexosaminidase activity with genetic analysis. Results: We identified a total of seven different mutations, three of which were novel (one in the HEXA gene and two in the HEXB gene) in 14 patients. We found a high frequency of c.1100_1111del (p.Gly367_Tyr370del) mutation in HEXA affected patients. The mean age at diagnosis was 13.46.3 months and 14.24.2 months for patients with Tay–Sachs disease (TSD) and Sandhoff disease (SD) respectively. Neuroregression was present in 92.9% of our patients. Of the 14 patients, 11 had epilepsy, 10 had developmental delay, 6 had hyperacusis, 6 had cherry-red spots and 6 had macrocephaly, but none of the patients had organomegaly. Conclusion: GM2 gangliosidoses disease should be considered for children with developmental regression and/or delay. For early diagnosis, enzyme analysis and gene detection should be performed in children with suspected GM2 gangliosidoses in the presence of clinical findings.

Keywords

Lysosomal storage disorders , GM2 gangliosidoses , hexosaminidase , Tay-Sachs disease , Sandhoff disease

Kaynakça

  1. 1. Leal AF, Benincore-Florez E, Solano-Galarza D, et al. GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. Int J Mol Sci 2020;21(17). DOI: 10.3390/ijms21176213.
  2. 2. Gort L, de Olano N, Macias-Vidal J, Coll MA, Spanish GMWG. GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients. Gene 2012;506(1):25-30. DOI: 10.1016/j.gene.2012.06.080.
  3. 3. Cachon-Gonzalez MB, Zaccariotto E, Cox TM. Genetics and Therapies for GM2 Gangliosidosis. Curr Gene Ther 2018;18(2):68-89. DOI: 10.2174/1566523218666180404162622.
  4. 4. Er E CE, Yazıcı H, Eraslan C, Sözmen E, Kalkan Uçar S, Çoker M. An Evalution of the Demographic and Clinical Characterictics of Patients with GM2 Gangliosidosis. . J Pediatr Res 2018;5:12-16.
  5. 5. Masingue M, Dufour L, Lenglet T, et al. Natural History of Adult Patients with GM2 Gangliosidosis. Ann Neurol 2020;87(4):609-617. DOI: 10.1002/ana.25689.
  6. 6. Virgolini MJ, Feliziani C, Cambiasso MJ, Lopez PH, Bollo M. Neurite atrophy and apoptosis mediated by PERK signaling after accumulation of GM2-ganglioside. Biochim Biophys Acta Mol Cell Res 2019;1866(2):225-239. DOI: 10.1016/j.bbamcr.2018.10.014.
  7. 7. Karimzadeh P, Jafari N, Nejad Biglari H, et al. GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series). Iran J Child Neurol 2014;8(3):55-60. (https://www.ncbi.nlm.nih.gov/pubmed/25143775).
  8. 8. Jain A, Kohli A, Sachan D. Infantile Sandhoff's disease with peripheral neuropathy. Pediatr Neurol 2010;42(6):459-61. DOI: 10.1016/j.pediatrneurol.2010.02.007.
  9. 9. Venugopalan P, Joshi SN. Cardiac involvement in infantile Sandhoff disease. J Paediatr Child Health 2002;38(1):98-100. DOI: 10.1046/j.1440-1754.2002.00765.x.
  10. 10. Sheth J, Datar C, Mistri M, Bhavsar R, Sheth F, Shah K. GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review. BMC Pediatr 2016;16:88. DOI: 10.1186/s12887-016-0626-6.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Klinik Tıp Bilimleri

Bölüm

Araştırma Makalesi

Yazarlar

Bilge Sarıkepe Bu kişi benim
0000-0003-3358-042X
Türkiye

Yayımlanma Tarihi

30 Eylül 2021

Gönderilme Tarihi

31 Mayıs 2021

Kabul Tarihi

2 Temmuz 2021

Yayımlandığı Sayı

Yıl 2021 Cilt: 46 Sayı: 3

DOI

https://doi.org/10.17826/cumj.945717

IZ

https://izlik.org/JA38BT52MS

Kaynak Göster

RIS / Bibtex
MLA
Bilginer Gürbüz, Berrak, vd. “GM2 gangliosidoses: evaluation of clinical, biochemical and genetic findings of patients with three novel mutations”. Cukurova Medical Journal, c. 46, sy 3, Eylül 2021, ss. 1201-7, doi:10.17826/cumj.945717.
Creative Commons Lisansı