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Mutations in GMPPB Presenting with Pseudometabolic Myopathy

  • Chiara Panicucci
  • Chiara Fiorillo
  • Francesca Moro
  • Guja Astrea
  • Giacomo Brisca
  • Federica Trucco
  • Marina Pedemonte
  • Paola Lanteri
  • Lucia Sciarretta
  • Carlo Minetti
  • Filippo M. Santorelli
  • Claudio BrunoEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 38)

Abstract

Mutations in the guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) gene encoding a key enzyme of the glycosylation pathway have been described in families with congenital (CMD) and limb girdle (LGMD) muscular dystrophy with reduced alpha-dystroglycan (α-DG) at muscle biopsy.

Patients typically display a combined phenotype of muscular dystrophy, brain malformations, and generalized epilepsy. However, a wide spectrum of clinical severity has been described ranging from classical CMD presentation to children with mild, yet progressive LGMD with or without intellectual disability. Cardiac involvement, including a long QT interval and left ventricular dilatation, has also been described in four cases.

Two missense mutations in GMPPB gene, one novel and one already reported, have been identified in a 21-year-old man presenting with elevated CK (38,650 UI/L; normal values <150 UI/L) without overt muscle weakness. Major complaints included limb myalgia, exercise intolerance, and several episodes of myoglobinuria consistent with a form of metabolic myopathy. Muscle biopsy showed only minimal alterations, whereas a marked reduction of glycosylated α-DG was evident.

This case further expands the phenotypic spectrum of GMPPB mutations and highlights the importance of exhaustive molecular characterization of patients with reduced glycosylation of α-DG at muscle biopsy.

Notes

Acknowledgments

The authors wish to thank the patient and his family for the collaboration, and Paolo Broda and Annagloria Incontrera for technical assistance.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Chiara Panicucci
    • 1
    • 2
  • Chiara Fiorillo
    • 2
    • 3
  • Francesca Moro
    • 4
  • Guja Astrea
    • 4
  • Giacomo Brisca
    • 1
  • Federica Trucco
    • 3
  • Marina Pedemonte
    • 3
  • Paola Lanteri
    • 5
  • Lucia Sciarretta
    • 5
  • Carlo Minetti
    • 2
    • 3
  • Filippo M. Santorelli
    • 4
  • Claudio Bruno
    • 1
    Email author
  1. 1.Center of Myology and Neurodegenerative Disorders, Department of Neuroscience and RehabilitationIstituto Giannina GasliniGenoaItaly
  2. 2.University of GenoaGenoaItaly
  3. 3.Pediatric Neurology UnitIstituto Giannina GasliniGenoaItaly
  4. 4.Neuromuscular and Molecular Medicine UnitIRCCS Stella Maris FoundationPisaItaly
  5. 5.Infantile Neuropsychiatry Unit, Department of Neuroscience and RehabilitationIstituto Giannina GasliniGenoaItaly

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