Prevalence and Novel Mutations of Lysosomal Storage Disorders in United Arab Emirates

LSD in UAE
  • Fatma A. Al-Jasmi
  • Nafisa Tawfig
  • Ans Berniah
  • Bassam R. Ali
  • Mahmoud Taleb
  • Jozef L. Hertecant
  • Fatma Bastaki
  • Abdul-Kader Souid
Research Report
Part of the JIMD Reports book series (JIMD, volume 10)

Abstract

Lysosomal storage disorders (LSD) are rare entities of recessive inheritance. The presence of a “founder” mutation in isolated communities with a high degree of consanguinity (e.g., tribes in the Middle East North Africa, MENA, region) is expected to lead to unusually high disease prevalence. The primary aim of this study was to estimate the prevalence of LSD and report their mutation spectrum in UAE. Between 1995 and 2010, 119 patients were diagnosed with LSD (65 Emiratis and 54 non-Emiratis). Genotyping was performed in 59 (50 %) patients (39 Emirati from 17 families and 20 non-Emiratis from 17 families). The prevalence of LSD in Emiratis was 26.9/100,000 live births. Sphingolipidoses were relatively common (9.8/100,000), with GM1-gangliosidosis being the most prevalent (4.7/100,000). Of the Mucopolysaccharidoses VI, IVA and IIIB were the predominant subtypes (5.5/100,000). Compared to Western countries, the prevalence of fucosidosis, Batten disease, and α-mannosidosis was 40-, sevenfold, and fourfold higher in UAE, respectively. The prevalence of Pompe disease (2.7/100,000) was similar to The Netherlands, but only the infantile subtype was found in UAE. Sixteen distinct LSD mutations were identified in 39 Emirati patients. Eight (50 %) mutations were reported only in Emirati, of which three were novel [c.1694G>T in the NAGLU gene, c.1336 C>T in the GLB1 gene, and homozygous deletions in the CLN3 gene]. Twenty-seven (42 %) patients were clustered in five of the 70 Emirati tribes. These findings highlight the need for tribal-based premarital testing and genetic counseling.

References

  1. Alfonso P, Rodriguez-Rey JC et al (2004) Expression and functional characterization of mutated glucocerebrosidase alleles causing Gaucher disease in Spanish patients. Blood Cells Mol Dis 32(1):218–225PubMedCrossRefGoogle Scholar
  2. Al-Gazali LI, Bener A et al (1997) Consanguineous marriages in the United Arab Emirates. J Biosoc Sci 29(4):491–497PubMedCrossRefGoogle Scholar
  3. Ali BR, Hertecant JL et al (2011) New and known mutations associated with inborn errors of metabolism in a heterogeneous Middle Eastern population. Saudi Med J 32(4):353–359PubMedGoogle Scholar
  4. Al-Jasmi F (2012) A novel mutation in an atypical presentation of the rare infantile Farber disease. Brain Dev 34(6):533–535PubMedCrossRefGoogle Scholar
  5. Bach G, Moskowitz SM et al (1993) Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area. Am J Hum Genet 53(2):330–338PubMedGoogle Scholar
  6. Beesley CE, Young EP et al (1998) 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 35(11):910–914PubMedCrossRefGoogle Scholar
  7. Ben-Rebeh I, Hertecant J L et al Identification of Mutations Underlying 20 Inborn Errors of Metabolism in the United Arab Emirates Population. Genet Test Mol Biomarkers May;16(5):366–371, 2012Google Scholar
  8. Bunge S, Knigge A et al (1999) Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha-N-acetylglucosaminidase gene mutations. J Med Genet 36(1):28–31PubMedGoogle Scholar
  9. Dionisi-Vici C, Rizzo C et al (2002) Inborn errors of metabolism in the Italian pediatric population: a national retrospective survey. J Pediatr 140(3):321–327PubMedCrossRefGoogle Scholar
  10. Eng CM, Desnick RJ (1994) Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene. Hum Mutat 3(2):103–111PubMedCrossRefGoogle Scholar
  11. Georgiou T, Drousiotou A et al (2004) Four novel mutations in patients from the Middle East with the infantile form of GM1-gangliosidosis. Hum Mutat 24(4):352PubMedCrossRefGoogle Scholar
  12. Harmon DL, Gardner-Medwin D et al (1993) Two new mutations in a late infantile Tay-Sachs patient are both in exon 1 of the beta-hexosaminidase alpha subunit gene. J Med Genet 30(2):123–128PubMedCrossRefGoogle Scholar
  13. Karageorgos L, Harmatz P et al (2004) Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy. Hum Mutat 23(3):229–233PubMedCrossRefGoogle Scholar
  14. Kroos M, Pomponio RJ et al (2008) Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum Mutat 29(6):E13–E26PubMedCrossRefGoogle Scholar
  15. Kudo M, Brem MS et al (2006) Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits precursor gene. Am J Hum Genet 78(3):451–463PubMedCrossRefGoogle Scholar
  16. Lan MY, Lin SJ et al (2009) A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease. Ann Hematol 88(7):695–697PubMedCrossRefGoogle Scholar
  17. Meikle PJ, Hopwood JJ et al (1999) Prevalence of lysosomal storage disorders. JAMA 281(3):249–254PubMedCrossRefGoogle Scholar
  18. Ozkara HA, Topcu M (2004) Sphingolipidoses in Turkey. Brain Dev 26(6):363–366PubMedCrossRefGoogle Scholar
  19. Pinto R, Caseiro C et al (2004) Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 12(2):87–92PubMedCrossRefGoogle Scholar
  20. Poorthuis BJ, Wevers RA et al (1999) The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 105(1–2):151–156PubMedGoogle Scholar
  21. Poupetova H, Ledvinova J et al (2010) The birth prevalence of lysosomal storage disorders in the Czech Republic: comparison with data in different populations. J Inherit Metab Dis 33(4):387–396PubMedCrossRefGoogle Scholar
  22. Raas-Rothschild A, Cormier-Daire V et al (2000) Molecular basis of variant pseudo-hurler polydystrophy (mucolipidosis IIIC). J Clin Invest 105(5):673–681PubMedCrossRefGoogle Scholar
  23. Weber B, Guo XH et al (1999) Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. Eur J Hum Genet 7(1):34–44PubMedCrossRefGoogle Scholar
  24. Zhang ZX, Wakamatsu N et al (1994) Impact of premature stop codons on mRNA levels in infantile Sandhoff disease. Hum Mol Genet 3(1):139–145PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Fatma A. Al-Jasmi
    • 1
  • Nafisa Tawfig
    • 2
  • Ans Berniah
    • 3
  • Bassam R. Ali
    • 4
  • Mahmoud Taleb
    • 2
  • Jozef L. Hertecant
    • 3
  • Fatma Bastaki
    • 5
  • Abdul-Kader Souid
    • 1
  1. 1.Department of PediatricsUnited Arab Emirates UniversityAl-AinUAE
  2. 2.Department of GeneticsLatifa HospitalDubaiUAE
  3. 3.Tawam HospitalAl-AinUAE
  4. 4.Department of PathologyUnited Arab Emirates UniversityAl-AinUAE
  5. 5.Department of PediatricsLatifa HospitalDubaiUAE

Personalised recommendations