Effect of a Mitochondrial Genetic Variant on Sevoflurane Hypersensitivity
10 Jun, 2026
Five years ago, a research project began that is now influencing anesthetic practice worldwide. It all started when Dr. Yaremy Hernández contacted Professor Eduardo Ruiz-Pesini, principal investigator of the U727 group at the Spanish Network Center for Biomedical Research on Rare Diseases (CIBERER), to discuss a troubling clinical case: two previously healthy children who developed severe neurological deterioration after undergoing general anesthesia.
In both patients, anesthesia triggered rapid degeneration of the basal ganglia, a brain region essential for motor control, leading to severe movement disorders. The children lost the ability to walk and became dependent on wheelchairs.
Analysis of their mitochondrial DNA (mtDNA) revealed that both carried the same rare genetic variant: the m.11232T>C transition. The situation became even more striking when Professor Ruiz-Pesini realized that years earlier he had encountered another highly similar case associated with the same variant.
The three children shared several remarkable characteristics. None had shown neurological problems before anesthesia, and all had Venezuelan maternal ancestry. However, the cases had occurred in completely different settings: the surgical procedures took place in different years (2005, 2016, and 2020) and in different countries (Germany, the United States, and Venezuela). This coincidence ruled out the possibility of a defective anesthetic batch.
From that point on, an international search for similar cases began. The team identified four additional patients who developed the same neurological syndrome following general anesthesia. All shared the same Venezuelan maternal ancestry and the same mitochondrial genetic variant.
The issue gained international attention in the summer of 2025, when the Chilean Society of Anesthesiology learned about the Zaragoza group’s findings and reported seven very similar cases in Chile, most of which had unfortunately resulted in death.
Since then, additional patients have been identified in Venezuela, Chile, the United States, and Spain. All display the same pattern: Venezuelan ancestry, the m.11232T>C mitochondrial DNA variant, and previous exposure to general anesthesia.
The first results of the study, now presented by Dr. Ruiz-Pesini’s team, point to a possible explanation. The research demonstrates that this genetic variant makes cells particularly sensitive to the inhaled anesthetic sevoflurane. In these patients, the drug can trigger an abrupt failure of cellular respiration, drastically reducing the cells’ ability to produce energy. However, the variant does not appear to alter the response to intravenously administered anesthetics.
The discovery is already having practical implications. Anesthesiology societies in several countries – including Venezuela, Chile, the United States, Canada, Spain, and other European countries – have begun issuing recommendations on the anesthetic management of patients of Venezuelan ancestry who require general anesthesia.
Meanwhile, the research group continues to study the effects of other inhaled anesthetics and different intravenous drugs in order to identify which agents can be used safely in these patients and to prevent similar cases from occurring again.
Reference