title: Limb-girdle myasthenia with tubular aggregates associated with novel GFPT1 mutations.
abstract: BACKGROUND
  Limb-girdle myasthenia with tubular aggregates (LGM with TAs) is a subtype of congenital myasthenic syndrome caused by recessive mutations of glutamine-fructose-6-phosphate transaminase 1 (GFPT1).
  
  
  METHODS
  Clinical and neurophysiological assessment was made in a Korean boy who had proximal limb muscle weakness. Findings suggested a diagnosis of congenital myasthenic syndrome.
  
  
  RESULTS
  Muscle biopsy disclosed numerous TAs in muscle fibers, and DNA sequence analysis disclosed 2 novel missense mutations (p.E256Q and p.M499T) in GFPT1. Treatment with oral cholinesterase inhibitors produced a dramatic improvement in muscle strength.
  
  
  CONCLUSIONS
  GFPT1 is the key enzyme in the hexosamine biosynthesis pathway, and mutations in GFPT1 cause defective glycosylation in the proteins of the neuromuscular junction. Identification of LGM with TAs among patients with congenital myasthenic syndrome is important because treatment with cholinesterase inhibitors can produce symptomatic improvement.
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Kumo-ro 20, Beomo-ri, Mulgum-eup, Yangsan, Gyeongnam 626-770, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Huh
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Ho-Jung
authors.initials: HJ
authors.lastname: Jang
authors.forename: Yeong-Eun
authors.initials: YE
authors.lastname: Park
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000235:genetics*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology*; D020294:Myasthenic Syndromes, Congenital / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D009469:Neuromuscular Junction / Q000201:enzymology* / Q000473:pathology; D010375:Pedigree
chemical_list: C497511:GFPT1 protein, human; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)