AARS2-related Leukodystrophy Without Ovarian Failure Mimicking Multiple Sclerosis in a Female: A Case Report With a Novel Pathogenic Variant (P4-12.010)

Abstract

<h3>Objective:</h3> N/A <h3>Background:</h3> <i>AARS2</i> mutations affect mitochondrial alanyl-transfer RNA (tRNA) synthetase. This enzyme is responsible of charging alanine to its cognate tRNA for protein translation within mitochondria. Individuals with <i>AARS2</i> mutations were reported to present either severe infantile cardiomyopathy or progressive leukoencephalopathy as the main clinical presentation. <i>AARS2</i>-related leukoencephalopathy is an ultra-rare white matter disorder, characterized by spasticity, ataxia, and impaired cognition. Further disease progression manifests as psychiatric illness and executive dysfunction. Ovarian failure is reported in almost all females with <i>AARS2</i>-related leukoencephalopathy. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 32-year-old female was referred to the clinic due to the development of progressive neurological symptoms since 2011. Ascending numbness of the lower limbs was the first clinical symptom that further extended to her abdomen. Patient, then, developed visual impairment in both eyes. Other symptoms included cognitive decline and language impairment that began abruptly with fast progression. She has one child and her menstrual cycles have been always regular. Multiple sclerosis was initially diagnosed and she was treated with corticosteroid, natalizumab, and rituximab without achieving improvements. The brain magnetic resonance imaging (MRI) of a patient performed in our institute showed multiple focal and confluent areas of diffusion restriction in bilateral periventricular and deep white matter, involving bilateral centrum semiovale/ corona radiate. Diffuse brain volume loss and bilateral thinning of optic nerves were observed. The MRI of thoracic spinal cord showed non-enhancing short segment T2 hyperintense lesions within the right ventral cord at T8-T9 and T12-L1. Molecular study reported a novel homozygous variant of c.929G&gt;T (p.Gly310Val) in <i>AARS2</i>. <h3>Conclusions:</h3> <i>AARS2</i>-related leukoencephalopathy in females can present without ovarian failure. The overlapping clinical and imaging features of white matter disorders may lead to misdiagnosis of the disease. Detailed review of clinical characteristics, MRI patterns, and molecular study can be helpful to reach to an accurate diagnosis. <b>Disclosure:</b> Mr. Amanat has nothing to disclose. Julie Cohen, 377 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Julie Cohen, 377 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Illumina. The institution of Julie Cohen, 377 has received research support from A Cure for Ellie. Dr. Fatemi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bluebirdbio. Dr. Fatemi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for RCO law. The institution of Dr. Fatemi has received research support from Minoryx. The institution of Dr. Fatemi has received research support from Viking Therapeutics. The institution of Dr. Fatemi has received research support from Swanbio Therapeutics . The institution of Dr. Fatemi has received research support from Autobahn Therapeutics. The institution of Dr. Fatemi has received research support from Nuvelution. The institution of Dr. Fatemi has received research support from NIH. The institution of Dr. Fatemi has received research support from A Cure for Ellie Foundation. The institution of Dr. Fatemi has received research support from Brian’s Hope Foundation . Dr. Fatemi has received intellectual property interests from a discovery or technology relating to health care. Dr. Fatemi has a non-compensated relationship as a Director (Board member) with ALDConnect that is relevant to AAN interests or activities. The institution of Dr. Fine has received research support from NIH.