Congenital myasthenic syndrome associated with episodic apnea and sudden infant death

Byring, Roger; Pihko, Helena; Tsujino, Akira; Shen, Xin Ming; Bi, Guorong; Hackman, Peter; Ohno, Kinji; Engel, Andrew G.; Udd, Bjarne

doi:10.1016/s0960-8966(01)00336-4

Cited by 73 publications

(56 citation statements)

References 25 publications

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“…Parents of affected children must be indoctrinated to anticipate sudden worsening of the weakness and possible apnea with febrile illnesses, excitement, or overexertion. Long-term nocturnal apnea monitoring is indicated in any patient in whom ChAT deficiency is proven or suspected (Byring et al, 2002).…”

Section: Cms With Episodic Apnea Due To Defects In Choline Acetyltranmentioning

confidence: 99%

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

Ohno¹,

Ito²,

Engel³

2012

Neuromuscular Disorders

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Section: Cms With Episodic Apnea Due To Defects In Choline Acetyltranmentioning

confidence: 99%

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

Ohno¹,

Ito²,

Engel³

2012

Neuromuscular Disorders

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“…Studies using biochemical and pharmacological approaches indicate that cholinergic nerve terminals may contain ChAT activity in kinetic excess of what is needed to support normal synthesis of ACh (for review, see Blusztajn and Wurtman, 1983), and two recent observations in vivo are consistent with this notion. In humans, polymorphism of the CHAT gene underlies the etiology of one form of presynaptic congenital myasthenic syndrome (CMS) designated as CMS with episodic apnea (CMS-EA) (Ohno et al, 2001;Byring et al, 2002). In this disease, the affected individuals inherit two abnormal CHAT alleles.…”

Section: Introductionmentioning

confidence: 99%

Choline Transporter 1 Maintains Cholinergic Function in Choline Acetyltransferase Haploinsufficiency

Brandon¹,

Mellott²,

Pizzo³

et al. 2004

J. Neurosci.

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Choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine (ACh), is thought to be present in kinetic excess in cholinergic neurons. The rate-limiting factor in ACh production is the provision of choline to ChAT. Cholinergic neurons are relatively unique in their expression of the choline transporter 1 (CHT1), which exhibits high-affinity for choline and catalyzes its uptake from the extracellular space to the neuron. Multiple lines of evidence indicate that the activity of CHT1 is a key determinant of choline supply for ACh synthesis. We examined the interaction of ChAT and ChT activity using mice heterozygous for a null mutation in the Chat gene (Chatϩ/Ϫ). In these mice, brain ChAT activity was reduced by 40 -50% relative to the wild type, but brain ACh levels as well as ACh content and depolarization-evoked ACh release in hippocampal slices were normal. However, the amount of choline taken up by CHT1 and ACh synthesized de novo from choline transported by CHT1 in hippocampal slices, as well as levels of CHT1 mRNA in the septum and CHT1 protein in several regions of the CNS, were 50 -100% higher in Chatϩ/Ϫ than in Chatϩ/ϩ mice. Thus, haploinsufficiency of ChAT leads to an increased expression of CHT1. Increased ChT activity may compensate for the reduced ChAT activity in Chatϩ/Ϫ mice, contributing to the maintenance of apparently normal cholinergic function as reflected by normal performance of these mice in several behavioral assays.

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“…2 Patients with recurrent apneas should have apnea monitor and home ventilator therapy (table 1). 6 Synaptic basal lamina. AChE deficiency.…”

Section: Go To Section 4 E160mentioning

confidence: 99%

Clinical Reasoning: A child with delayed motor milestones and ptosis

Ghosh

2017

Neurology

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Congenital myasthenic syndrome associated with episodic apnea and sudden infant death

Cited by 73 publications

References 25 publications

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

Choline Transporter 1 Maintains Cholinergic Function in Choline Acetyltransferase Haploinsufficiency

Clinical Reasoning: A child with delayed motor milestones and ptosis

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