Abstract Details

Title Spinal Muscular Atrophy Mimicking Adult-onset GM2 Gangliosidosis AB variant: A Case Report

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 052

Objective To describe a patient diagnosed with rare adult-onset GM2 gangliosidosis AB variant by whole exome sequencing.

Background GM2 gangliosidoses are a group of metabolic disorders caused by lysosomal accumulation of glycolipids. There are three variants of GM2 gangliosidoses: Tay–Sachs disease (TSD), Sandhoff disease, and GM2-gangliosidosis AB variant. The latter is characterized by normal hexosaminidase A/B, but the inability to form a functional GM2 activator complex. The clinical phenotype of the AB variant is similar to “HEXA-related” TSD. Symptoms in the adult vary, are less severe than the infantile form, and can present gradually. Symptoms include tremors, fasciculations, and ataxia. Spinal muscular atrophy type III patients develop normally until adolescence, when proximal muscle weakness appears.

Design/Methods Retrospective chart review and literature search.

Results 36-year-old woman with a history of progressive muscle weakness, restrictive lung disease, and a clinical diagnosis of SMA type III was referred to neurogenetics. Her symptoms began at 21 years of age with frequent falls which progressed to trouble climbing steps and walking long distances. She was diagnosed with SMA type III at 24 years of age based on clinical features and ancillary testing (EMG/NCS and muscle biopsy) showing findings suggestive of a progressive motor neuron disease, but with negative homozygous deletion of exon 7 and MFN2 sequencing. Clinical exam significant for her being wheelchair bound with MRC Grade 2-3/5 strength in bilateral lower extremities and 4/5 in bilateral upper extremities. Whole exome sequencing revealed a homozygous variant of uncertain significance in GM2A c.346G>C (p.D116H) inherited from her parents. The GM2A gene associated with the AB type of GM2 gangliosidosis. Enzyme testing was normal for hexosaminidase A & B.

Conclusions Due to late onset and slow progression of symptoms, diagnosis of adult onset GM2 gangliosidoses is often overlooked.

Authors/Disclosures
Zachary Klopman PRESENTER	Mr. Klopman has nothing to disclose.
Prashant Natteru, MBBS (Mayo Clinic Health System)	Dr. Natteru has nothing to disclose.
Saurabh G. Shukla, MD (Lone Star Neurology)	Dr. Shukla has nothing to disclose.
Kimberly R. McDonald, MD	Dr. McDonald has nothing to disclose.

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Abstract Details