Abstract Details

Title FUS Associated Familial Amyotrophic Lateral Sclerosis Mimicking a Limb Girdle Muscular Dystrophy Phenotype

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P7 - Poster Session 7 (5:30 PM-6:30 PM)

Poster/Presentation
Number 1-004

Objective To present a case of genetically confirmed amyotrophic lateral sclerosis (ALS) due to pathogenic variant in FUS mimicking a limb girdle muscular dystrophy at disease onset.

Background ALS is a devastating progressive degenerative disorder affecting the motor neurons. Most cases are sporadic but familial inheritance accounts for approximately 10% of cases. Phenotypically, the most common presentation is single distal limb weakness with eventual spread.

Design/Methods NA

Results A 31-year-old Caucasian female with a history of post-partum cardiomyopathy presented to the emergency department for a 7-month history of progressive neck and proximal, symmetrical muscle weakness with upper limb predominance. Initial neurological examination revealed mildly increased reflexes at the brachioradialis and patella, but no identifiable pathologic reflexes. Electromyography (EMG) showed normal sensory and motor nerve conductions, with membrane irritability in multiple muscle groups. Serum creatinine kinase was normal. A working differential of myopathy prompted a muscle biopsy which discovered chronic neurogenic changes. Subsequently, three weeks after original presentation, the patient represented for orthopnea requiring non-invasive positive pressure ventilatory support. Interval examination revealed progressive neck weakness, and new brisk reflexes notable for positive cross adduction, Hoffman, and Babinski. She also developed shoulder atrophy, and lower extremity fasciculations with cramping. Repeat EMG showed chronic and active denervation. Ultimately, genetic testing revealed autosomal dominant pathologic variant in the FUS gene, consistent with early onset ALS.

Conclusions FUS is a multifunctional protein involved with RNA binding, splicing, and transport between the nucleus and cytoplasm. Dysfunction of FUS likely produces pathological effects on motor neurons, leading to a rare form of ALS. Our case highlights the vast clinical spectrum of ALS, as this patient’s pattern of weakness and atrophy is similar to many of the earliest reported families with this mutation. Furthermore, this case emphasized the benefit of genetic testing as a method to support the diagnosis of motor neuron disease.

Authors/Disclosures
Hera A. Kamdar, MD PRESENTER	Dr. Kamdar has nothing to disclose.
	No disclosure on file
Miriam L. Freimer, MD, FAAN (The Ohio State University)	Dr. Freimer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for alexion. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for J and J. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Freimer has received research support from Alnylum. The institution of Dr. Freimer has received research support from UCB. The institution of Dr. Freimer has received research support from NIH. The institution of Dr. Freimer has received research support from Janssen. Dr. Freimer has received research support from Avidity. Dr. Freimer has received research support from Fulcrum. The institution of Dr. Freimer has received research support from Dept of defense. The institution of an immediate family member of Dr. Freimer has received research support from Abcurro. Dr. Freimer has received personal compensation in the range of $10,000-$49,999 for serving as a presentations/teaching with UCB.
Bakri Elsheikh, MD, FAAN (The Ohio State University Wexner Medical Center)	Dr. Elsheikh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen . Dr. Elsheikh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argnex . The institution of Dr. Elsheikh has received research support from Biogen. The institution of Dr. Elsheikh has received research support from Cure SMA.
Jennifer A. Roggenbuck, MS, CGC (Ohio State University)	The institution of Ms. Roggenbuck has received research support from Packard Foundation.
Adam Quick, MD (The Ohio State University)	The institution of Dr. Quick has received research support from NINDS. The institution of Dr. Quick has received research support from NEALS.

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