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Tytuł:
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Clinical features of the myasthenic syndrome arising from mutations in GMPPB.
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Autorzy:
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Rodríguez Cruz, Pedro M.
Belaya, Katsiaryna
Basiri, Keivan
Sedghi, Maryam
Farrugia, Maria Elena
Holton, Janice L.
Wei Wei Liu
Maxwell, Susan
Petty, Richard
Walls, Timothy J.
Kennett, Robin
Pitt, Matthew
Sarkozy, Anna
Parton, Matt
Lochmüller, Hanns
Muntoni, Francesco
Palace, Jacqueline
Beeson, David
Liu, Wei Wei
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Temat:
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CONGENITAL myasthenic syndromes
GENETIC mutation
GLYCOSYLATION
NEUROMUSCULAR transmission
CREATINE kinase
MUSCLE disease treatment
DYSTROGLYCAN
ALBUTEROL
MEMBRANE proteins
MYASTHENIA gravis
RESEARCH funding
NUCLEOTIDYLTRANSFERASES
DIAGNOSIS
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Źródło:
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Journal of Neurology, Neurosurgery & Psychiatry; Aug2016, Vol. 87 Issue 8, p802-809, 8p, 1 Color Photograph, 2 Diagrams, 2 Charts, 2 Graphs
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Background: Congenital myasthenic syndrome (CMS) due to mutations in GMPPB has recently been reported confirming the importance of glycosylation for the integrity of neuromuscular transmission.Methods: Review of case notes of patients with mutations in GMPPB to identify the associated clinical, neurophysiological, pathological and laboratory features. In addition, serum creatine kinase (CK) levels within the Oxford CMS cohort were retrospectively analysed to assess its usefulness in the differential diagnosis of this new entity.Results: All patients had prominent limb-girdle weakness with minimal or absent craniobulbar manifestations. Presentation was delayed beyond infancy with proximal muscle weakness and most patients recall poor performance in sports during childhood. Neurophysiology showed abnormal neuromuscular transmission only in the affected muscles and myopathic changes. Muscle biopsy showed dystrophic features and reduced α-dystroglycan glycosylation. In addition, myopathic changes were present on muscle MRI. CK was significantly increased in serum compared to other CMS subtypes. Patients were responsive to pyridostigimine alone or combined with 3,4-diaminopyridine and/or salbutamol.Conclusions: Patients with GMPPB-CMS have phenotypic features aligned with CMS subtypes harbouring mutations within the early stages of the glycosylation pathway. Additional features shared with the dystroglycanopathies include myopathic features, raised CK levels and variable mild cognitive delay. This syndrome underlines that CMS can occur in the absence of classic myasthenic manifestations such as ptosis and ophthalmoplegia or facial weakness, and links myasthenic disorders with dystroglycanopathies. This report should facilitate the recognition of this disorder, which is likely to be underdiagnosed and can benefit from symptomatic treatment. [ABSTRACT FROM AUTHOR]
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