Your browser doesn't support javascript.
loading
Clinical features of the myasthenic syndrome arising from mutations in GMPPB.
Rodríguez Cruz, Pedro M; Belaya, Katsiaryna; Basiri, Keivan; Sedghi, Maryam; Farrugia, Maria Elena; Holton, Janice L; Liu, Wei Wei; Maxwell, Susan; Petty, Richard; Walls, Timothy J; Kennett, Robin; Pitt, Matthew; Sarkozy, Anna; Parton, Matt; Lochmüller, Hanns; Muntoni, Francesco; Palace, Jacqueline; Beeson, David.
Afiliación
  • Rodríguez Cruz PM; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
  • Belaya K; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Basiri K; Neurology Department, Neuroscience Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Sedghi M; Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Farrugia ME; Department of Neurology, Institute of Neurological Sciences, The Queen Elizabeth University Hospital, Glasgow, UK.
  • Holton JL; Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
  • Liu WW; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Maxwell S; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Petty R; Department of Neurology, Institute of Neurological Sciences, The Queen Elizabeth University Hospital, Glasgow, UK.
  • Walls TJ; Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
  • Kennett R; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
  • Pitt M; Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
  • Sarkozy A; MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
  • Parton M; MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
  • Lochmüller H; Institute of Genetic Medicine, John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, UK.
  • Muntoni F; Dubowitz Neuromuscular Centre & MRC Centre for Neuromuscular Diseases, UCL Institute of Child Health, London, UK.
  • Palace J; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
  • Beeson D; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
J Neurol Neurosurg Psychiatry ; 87(8): 802-9, 2016 08.
Article en En | MEDLINE | ID: mdl-27147698
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 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Asunto principal: Síndromes Miasténicos Congénitos / Nucleotidiltransferasas Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurol Neurosurg Psychiatry Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Asunto principal: Síndromes Miasténicos Congénitos / Nucleotidiltransferasas Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurol Neurosurg Psychiatry Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido