Limb-girdle myasthenia with tubular aggregates associated with novel GFPT1 mutations

Authors

  • So-Young Huh MD,

    1. Department of Neurology, Pusan National University School of Medicine, Yangsan, Kumo-ro 20, Beomo-ri, Mulgum-eup, Yangsan, Gyeongnam 626-770, Republic of Korea
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  • Hyang-Sook Kim MSc,

    1. Research Institute for Convergence of Biomedical Research and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
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  • Ho-Jung Jang MSc,

    1. Research Institute for Convergence of Biomedical Research and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
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  • Yeong-Eun Park MD, PhD,

    1. Department of Neurology, Pusan National University School of Medicine, Yangsan, Kumo-ro 20, Beomo-ri, Mulgum-eup, Yangsan, Gyeongnam 626-770, Republic of Korea
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  • Dae-Seong Kim MD, PhD

    Corresponding author
    1. Department of Neurology, Pusan National University School of Medicine, Yangsan, Kumo-ro 20, Beomo-ri, Mulgum-eup, Yangsan, Gyeongnam 626-770, Republic of Korea
    2. Research Institute for Convergence of Biomedical Research and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
    • Department of Neurology, Pusan National University School of Medicine, Yangsan, Kumo-ro 20, Beomo-ri, Mulgum-eup, Yangsan, Gyeongnam 626-770, Republic of Korea
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Abstract

Introduction:

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. Muscle Nerve 46: 599–602, 2012

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