Abstract Details

Title Congenital Myasthenic Syndrome Due to Novel GFPT1 Variant Presenting with Head Drop and Visual Impairment: A Case Report

Topic Child Neurology and Developmental Neurology

Presentation(s) P9 - Poster Session 9 (5:00 PM-6:00 PM)

Poster/Presentation
Number 8-001

Objective Our objective is to describe a novel GFPT1 variant causing congenital myasthenic syndrome (CMS), expanding the clinical, pathologic, neurophysiological and genetic understanding of GFPT1-related CMS and emphasizing the importance of deep phenotyping a novel genotype.

Background GFPT1 gene variants are a known cause of CMS, typically presenting with fatigable limb-girdle weakness and characteristic tubular aggregates on muscle biopsy, though recent reports have broadened the clinical spectrum. GFPT1 encodes for glutamine-fructose-6-phosphate transaminase 1, an enzyme that catalyzes the initial and rate-determining step of the hexosamine biosynthetic pathway regulating the glycosylation of key neuromuscular junction (NMJ) proteins including acetylcholine receptor subunits. The pathogenic GFPT1 variants result in decreased NMJ acetylcholine receptor expression and impaired signaling.

Design/Methods We describe a 5-year-old boy presenting with hypotonia, progressive muscle weakness with head drop, cognitive delay, and visual impairment, found to have a novel homozygous missense variant in GFPT1 (c.1154G>A, p.R385Q). Upon further workup, neuroimaging showed white matter abnormalities with atrophy of corpus callosum and cerebellum, electromyography showed myopathic motor unit potentials, and muscle biopsy showed non-specific changes.

Results A stimulated jitter analysis (stim-JA) of the right orbicularis oculi muscle was performed. The Twenty apparent single fiber action potentials (ASFAPs) were recorded with mean jitter value of 69 µs (normal < 24 µs). 95% of ASFAPs (n=19) showed increased jitter and 55% (n=8) were blocked. The NMJ transmission defect on the stim-JA study confirmed the clinical and genetic suspicions of CMS.

Conclusions CMS can present broadly and can be diagnostically challenging due to its clinical overlap with other neuromuscular disorders. The index case underscores the importance of deep phenotyping a genotype based on suspected clinical presentation. The case also highlights glycosylation-related CMS and a muscle-eye-brain connection.

Authors/Disclosures
Katharine Torrey PRESENTER	Ms. Torrey has nothing to disclose.
Emmanuelle R. Tiongson, MD (Childrens Hospital Los Angeles)	Dr. Tiongson has nothing to disclose.
Rachel Logan	Rachel Logan has nothing to disclose.
John V. Dennison, MD	Dr. Dennison has nothing to disclose.
Andrew Fischer, MD	An immediate family member of Dr. Fischer has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for BrainQ Technologies.
Mansi Jain, MD, MBBS	Dr. Jain has nothing to disclose.
Matthew J. Schniederjan	Mr. Schniederjan has received publishing royalties from a publication relating to health care.
Ricardo A. Maselli, MD	Dr. Maselli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ARGENX. Dr. Maselli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst.
Sumit Verma, MD (Emory Children's Center)	Dr. Verma has nothing to disclose.

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