Recurrent Cerebral Ischemic Events in a Patient with a POLG Gene Mutation: A Case Report
Juan Sebastian Sanchez Léon1, Carolina Matté Dagostini1, TAIS DENICOL1, Renato Dumbá Monteiro De Castro1, Fernanda Nicoli Broch1, Pedro Hall Ruschel1, Karla Sarai Castro1
1Santa Casa de Porto Alegre Hospital
Objective:
Report a case of stroke-like events in a young patient with a mutation in the POLG gene, highlighting the differential diagnosis for recurrent cerebral ischemia.
Background:
Ischemic stroke is one of the leading causes of death globally. Major risk factors include hypertension, diabetes, and smoking, though genetic alterations play a role in some cases.
Design/Methods:
Not applicable.
Results:
Female patient, smoker, hypertense, and with a maternal familiar history of cerebrovascular disease. At 58 experienced her first vascular event. Diagnosed with hypertensive stroke, residual hemiparesis, and dysarthria as sequelae. A year later, she was rehospitalized due to worsening dysarthria. A CT scan revealed ischemic sequelae and severe microangiopathy, confirmed by MRI, which showed a recent ischemic event and Fazekas grade 3 microangiopathy. She was discharged with a presumptive CADASIL diagnosis. Her condition worsened over the following months, with functional decline, and behavioral changes. By age 61, she was fully dependent for daily activities and was rehospitalized for seizures and global aphasia. New ischemic lesions were found on imaging. Genetic testing ruled out NOTCH3 mutations but revealed a heterozygous variant of uncertain significance (VUS) in the DNA polymerase gamma (POLG) gene (c.752C>T, p.Thr251Ile), linked to mitochondrial function. The final diagnosis was a POLG-related disorder with stroke-like episodes. Due to the extensive ischemic damage and complete loss of function, palliative care was recommended.
Conclusions:
POLG is a human mitochondrial DNA polymerase, essential for maintaining DNA integrity. Mutations in the POLG gene are linked to syndromes such as Alpers-Huttenlocher syndrome; however, ischemic stroke is a rare manifestation. Similar to stroke-like episodes observed in MELAS (mitochondrial encephalopathy associated with lactic acidosis and stroke-like lesions), the pathophysiology may involve endothelial dysfunction. A definitive diagnosis requires genetic testing. Management is supportive, as demonstrated in this case. This report underscores the importance of considering genetic mutations in patients with recurrent ischemic events.
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