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.
“Chiara Panicucci” and “Chiara Fiorillo” equally contributed to this work.
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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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Communicated by: Jaak Jaeken, Em. Professor of Paediatrics
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Take Home Message
In this report we highlight the importance of considering an α-DG glycosylation defect when a pseudometabolic phenotype occurs.
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Chiara Panicucci, Chiara Fiorillo, Francesca Moro, Guja Astrea, Giacomo Brisca, Federica Trucco, Marina Pedemonte, Paola Lanteri, Lucia Sciarretta, Carlo Minetti, Filippo M. Santorelli, and Claudio Bruno declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
Author Contributions
Study concept and design: Panicucci, Fiorillo, Bruno.
Acquisition of data: Panicucci, Fiorillo, Moro, Astrea, Trucco, Lanteri, Sciarretta.
Analysis and interpretation of data: Panicucci, Fiorillo, Brisca, Pedemonte, Lanteri, Sciarretta, Bruno.
Drafting of the manuscript: Panicucci, Fiorillo, Pedemonte, Bruno.
Critical revision of the manuscript for important intellectual content: Fiorillo, Minetti, Santorelli, Bruno.
Obtained funding: Santorelli, Bruno.
Administrative, technical, and material support: Santorelli, Bruno.
Study supervision: Fiorillo, Bruno.
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Panicucci, C. et al. (2017). Mutations in GMPPB Presenting with Pseudometabolic Myopathy. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 38. JIMD Reports, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_25
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DOI: https://doi.org/10.1007/8904_2017_25
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