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Journal of Neurology

, Volume 256, Issue 11, pp 1881–1890 | Cite as

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations

  • Sueli M. Oba-Shinjo
  • Roseli da Silva
  • Fernanda G. Andrade
  • Rachel E. Palmer
  • Robert J. Pomponio
  • Kristina M. Ciociola
  • Mary S. Carvalho
  • Paulo S. Gutierrez
  • Gilda Porta
  • Carlo D. Marrone
  • Verônica Munoz
  • Anderson K. Grzesiuk
  • Juan C. LlerenaJr.
  • Célia R. Berditchevsky
  • Claudia Sobreira
  • Dafne Horovitz
  • Thamine P. Hatem
  • Elizabeth R. C. Frota
  • Rogerio Pecchini
  • João Aris Kouyoumdjian
  • Lineu Werneck
  • Veronica M. Amado
  • José S. CameloJr.
  • Robert J. Mattaliano
  • Suely K. N. MarieEmail author
Original Communication

Abstract

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid α-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.

Keywords

Acid α-glucosidase Pompe disease Glycogen storage disease type II Acid maltase deficiency Mutation analysis Novel mutation 

Notes

Acknowledgments

This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), grant number 2001/00422-5, and Genzyme Corporation.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sueli M. Oba-Shinjo
    • 1
  • Roseli da Silva
    • 1
  • Fernanda G. Andrade
    • 1
  • Rachel E. Palmer
    • 4
  • Robert J. Pomponio
    • 4
  • Kristina M. Ciociola
    • 4
  • Mary S. Carvalho
    • 1
  • Paulo S. Gutierrez
    • 2
  • Gilda Porta
    • 3
  • Carlo D. Marrone
    • 5
  • Verônica Munoz
    • 6
  • Anderson K. Grzesiuk
    • 7
  • Juan C. LlerenaJr.
    • 8
  • Célia R. Berditchevsky
    • 9
  • Claudia Sobreira
    • 10
  • Dafne Horovitz
    • 11
  • Thamine P. Hatem
    • 12
  • Elizabeth R. C. Frota
    • 13
  • Rogerio Pecchini
    • 14
  • João Aris Kouyoumdjian
    • 15
  • Lineu Werneck
    • 16
  • Veronica M. Amado
    • 17
  • José S. CameloJr.
    • 11
  • Robert J. Mattaliano
    • 18
  • Suely K. N. Marie
    • 1
    Email author
  1. 1.Myopathies and Molecular Biology Group, Department of Neurology, School of MedicineUniversity of São PauloSão PauloBrazil
  2. 2.Heart InstituteUniversity of São PauloSão PauloBrazil
  3. 3.Department of Pediatrics, School of MedicineUniversity of São PauloSão PauloBrazil
  4. 4.Clinical Laboratory Science, Molecular Genetic Analysis GroupGenzyme CorporationFraminghamUSA
  5. 5.Division of Pathology AnatomyClínica MarronePorto AlegreBrazil
  6. 6.Hospital das Clínicas de Porto AlegrePorto AlegreBrazil
  7. 7.Instituto Neurológico e da Coluna VertebralCuiabáBrazil
  8. 8.Instituto Fernandes Figueira, Fundação Oswaldo CruzRio de JaneiroBrazil
  9. 9.Hospital Servidores do Estado do Rio de JaneiroRio de JaneiroBrazil
  10. 10.Department of Neurology, Psychiatry and Medical PsychologyUniversity of São PauloRibeirão PretoBrazil
  11. 11.Department of Puericulture and Pediatrics, Ribeirão Preto School of MedicineUniversity of São PauloRibeirão PretoBrazil
  12. 12.Unidade de Cardiologia e Medicina FetalRecifeBrazil
  13. 13.Hospital das Clínicas Federal University of Minas GeraisBelo HorizonteBrazil
  14. 14.Santa Casa de Misericórdia Medical SchoolSão PauloBrazil
  15. 15.Department of Neurological SciencesSchool of Medicine of São José do Rio PretoSão PauloBrazil
  16. 16.Hospital das Clínicas do ParanáUniversity of ParanáCuritibaBrazil
  17. 17.School of MedicineUniversity of BrasiliaBrasiliaBrazil
  18. 18.Genzyme CorporationFraminghamUSA

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