(703) Atypical Metabolic Cause of Ischemic Stroke due to Aortic Thrombus: Homozygous MTHFR A1298C Mutation

Introduction: We report an unusual case of ischemic stroke in a middle age hispanic male with hyperhomocystenemia and vitamin B12 deficiency due to homozygous methylene tetrahydrofolate reductase (MTHFR) A1298C variant gene mutation.

Description: A 51-year-old Hispanic male with a history of hypertension presented with acute onset right-sided weakness, aphasia, right facial droop, and syncope. He had an initial NIHSS of 24, consistent with left MCA syndrome. Admission imaging with CT head was negative for acute intracranial abnormalities, but a CTA head/neck revealed a left M1 occlusion and an aortic arch thrombus. The patient received TNK three hours after symptom onset, leading to spontaneous recanalization of the left M1 thrombus as seen by a cerebral angiogram. MRI later showed acute infarcts throughout the left basal ganglia, along with additional punctate infarcts in the left subcortical and insular regions. Hypercoagulable workup revealed a homozygous MTHFR DNA mutation A1298C variant, along with a vitamin B12 level of 101 pg/mL, homocysteine level of 21.44 uMol/L, and methylmalonic acid level of 1187 nMol/L. Genetic testing confirmed the presence of the homozygous MTHFR DNA mutation A1298C variant. other hypercoagulable studies came back unremarkable. On hospital day 7, a transesophageal echocardiography (TEE) was negative for thrombus in the ascending aorta. The patient was discharged on hospital day 8 with Aspirin and a high dose atorvastatin.

Discussion: In our case, the patient presented with an acute ischemic stroke due to aorta thrombus embolization. Upon investigating other causes of thrombosis, all potential causes were ruled out except hyperhomocysteinemia. Further investigation revealed a positive homozygous MTHFR A1298C gene mutation, explaining the increased thrombotic events and stroke in this patient. This case highlights the importance of considering B12 deficiency, hyperhomocystenemia and genetic factors, such as the MTHFR A1298C mutation, in patients with unexplained thrombotic events and strokes. Early detection and management of hyperhomocysteinemia and B12 deficiency can play a crucial role in preventing further complications.