Toggle Main Menu Toggle Search

Open Access padlockePrints

Clinical features of the myasthenic syndrome arising from mutations in GMPPB

Lookup NU author(s): Dr Anna Sarkozy, Professor Hanns Lochmuller

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

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 a-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.


Publication metadata

Author(s): Cruz PMR, Belaya K, Basiri K, Sedghi M, Farrugia ME, Holton JL, Liu WW, Maxwell S, Petty R, Walls TJ, Kennett R, Pitt M, Sarkozy A, Parton M, Lochmuller H, Muntoni F, Palace J, Beeson D

Publication type: Article

Publication status: Published

Journal: Journal of Neurology Neurosurgery and Psychiatry

Year: 2016

Volume: 87

Issue: 8

Pages: 802-809

Print publication date: 01/08/2016

Online publication date: 04/05/2016

Acceptance date: 31/03/2016

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ Group

URL: http://dx.doi.org/10.1136/jnnp-2016-313163

DOI: 10.1136/jnnp-2016-313163


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share