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Abstract Details

Rapidly Progressive Amyotrophic Lateral Sclerosis in a Young Male with BRCA2 Variant
Neuromuscular and Clinical Neurophysiology (EMG)
P5 - Poster Session 5 (5:30 PM-6:30 PM)
11-018

To illustrate a case of rapidly progressive ALS (RPALS) in an adult with a BRCA2 pathogenic variant.

RPALS accounts for 5–10% of ALS cases and is a devastating disorder affecting motor neurons (MN). Although its etiology is poorly understood, mutations in DNA repair (BRCA), cellular homeostasis (C9orf72) and defense against oxygen toxicity (SOD1) in part determine MN fate and functional decline in ALS.

Brain-spine MRI, CSF (paraneoplastic, metagenomics testing), electromyography (EMG), whole exome sequencing (WES) and autopsy were performed.
A 31-year-old male, construction worker, with history of smoking and non-active polysubstance abuse, presented with seven months of right lower extremity weakness that progressed to flaccid paraplegia. He became wheelchair-bound and had right arm and truncal weakness within one month. Cognition was intact. He became quadriplegic in one month and subsequently presented with shortness of breath progressing to respiratory failure. Extubation was unsuccessful due to bulbar weakness. He had no response to empirical treatment with steroids and immunoglobulins. He underwent tracheostomy, gastrostomy and became ventilator dependent. Patient and family decided to withdraw care. He died fifteen months after symptoms onset. Inflammatory, toxic-metabolic and infectious workup was unrevealing. EMG showed widespread axonal injury (active and chronic denervation) to the anterior horn cells (AHC) and/or their axons. Imaging showed abnormal T2 signal in corticospinal tracts in brain and spinal cord. WES revealed mutated BRCA2 (c.4478_4481del, p.Glu1493fs). Autopsy showed severe astrogliosis and motoneuron loss in spinal cord and precentral gyrus, with very few residual (+) TDP-43 AHC.

RPALS is a poorly understood and fatal condition. We report a pathogenic BRCA2 mutation in a patient with RPALS. Animal studies have shown dysregulation of BRCA in microglia as a contributor of neurodegeneration. As a first step to examine BRCA2 involvement in human ALS, BRCA2 immunohistochemistry will be performed with this patient’s autopsy tissue.

Authors/Disclosures
Brahyan Galindo Mendez, MD, MPH (BWH, CART)
PRESENTER 		Dr. Galindo Mendez has nothing to disclose.
George Zanazzi No disclosure on file
Elijah Stommel, MD, FAAN (Dartmouth-Hitchock Med Ctr/Dept of Neuro) Dr. Stommel has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Suslick Attorney. The institution of Dr. Stommel has received research support from CDC.