A Zaragoza investigation identifies a genetic mutation in Venezuelan patients linked to severe neurological damage

The condition is inherited maternally and is rare. Scientific societies of anesthesiology have already begun to issue and disseminate specific clinical recommendations.

An international investigation developed over the last eight years and led by Professor Eduardo Ruiz Pesini, Professor of Biochemistry and researcher at the University of Zaragoza, has reached a scientific milestone of great impact for global anesthetic safety. The finding reveals that the m.11232T>C variant, found in some people of Venezuelan maternal origin, causes extreme hypersensitivity to sevoflurane. In response to this discovery, scientific societies of anesthesiology have issued special guidelines on how to manage patients of this nationality who are going to be exposed to general anesthetics.

The study directed by Ruiz Pesini, researcher of the Aragon Health Research Institute (IIS Aragon) and the Biomedical Research Network Center for Rare Diseases (Ciberer), explains the molecular basis by which a genetic variant in mitochondrial DNA predisposes to suffering severe neurological deterioration after undergoing procedures under general inhalation anesthesia with halogenated agents. 

The investigation began after clinical cases were detected of previously healthy pediatric patients who, after receiving general anesthesia in conventional surgeries, developed a Neurological injury with severe motor disorders, causing loss of the ability to walk. As Ruiz Pesini points out, "there could be up to 40 possible cases identified worldwide."

In 2018, he recalls, they received a sample from a patient in Barcelona "suspected of having a mitochondrial disease": "We analyzed it and found a mutation, but we couldn't characterize it." Two years later, the doctor Yaremy Hernández contacted the research group Professor Eduardo Ruiz Pesini, principal investigator of the Biogenesis and Mitochondrial Pathology group, recounts: “She told us about a disturbing clinical case: two healthy children who, after undergoing general anesthesia, had suffered severe neurological deterioration. In both cases, the anesthesia triggered rapid degeneration of the basal ganglia, a key brain region for movement control, which caused severe motor disorders. The children lost the ability to walk and became dependent on wheelchairs.” “When we contacted Barcelona again, they confirmed that the case they had referred to us involved a Venezuelan man who had also undergone surgery under anesthesia,” he explains. "So we started looking for patients with these characteristics all over the world."

Pathogenic mechanism and therapeutic alternative 

Experimental results demonstrate that the genetic transition m.11232T>C It alters cellular respiration in the presence of the inhalational anesthetic sevoflurane. When exposed to this drug, patients' cells experience acute failure that drastically reduces their ability to produce energy. Crucially, the study has confirmed that this variant does not alter the response to intravenously administered anesthetics at all, thus establishing a completely safe clinical alternative. 

By sequencing the mitochondrial DNA (mtDNA) of those affected, researchers They identified the presence of the rare genetic variant m.11232T>CThe investigation took a crucial turn when it was discovered that all The affected children shared an indispensable common link: they had a Venezuelan maternal origin. "The inheritance is transmitted maternally and it is a mutation that initially appears to be rare. We cannot yet say the exact frequency because we would need to expand our control population.«, he indicates. 

Despite the surgical interventions They were carried out in completely separate health and temporal contexts and in countries so far apart As in Germany, the United States, and Venezuela, the perfect genetic match allowed for the complete exclusion of accidental environmental factors, such as defective batches of anesthetic drugs, unequivocally redirecting the focus to inherited genetic susceptibility. 

The problem took on a global scale starting in the summer of 2025., when the Chilean Society of Anesthesiology reported the existence of seven cases with very similar symptoms in its territory, a number that has been increasing since the publication of the article. The search and medical surveillance network has identified new cases with the exact same pattern in Venezuela, Chile, the United States, and Spain.. 

Immediate impact on global anesthetic practice 

The significance of this discovery, led by the University of Zaragoza, lies in its immediate translation to practical preventive medicine. In order to prevent the recurrence of incidents of this nature, the main international scientific societies of anesthesiology—including those of Venezuela, Chile, the United States, Canada, Spain, as well as the European Society of Anesthesiology—have already begun to issue and disseminate specific clinical recommendations. These guidelines urge Evaluate the family history of patients of Venezuelan origin and adapt the anesthetic strategy, prioritizing the use of intravenous drugs. 

The research group at the University of Zaragoza continues his lines of study Analyzing the impact of other inhaled anesthetic agents and different intravenous formulations, with a firm commitment to defining a comprehensive guide to safe drugs that completely neutralizes the risks associated with this genetic condition worldwide. Furthermore, the scientific journal AnesthesiologyThe journal with the highest impact factor in the field of Anesthesiology has dedicated its cover and editorial to this finding.

Source: Heraldo de Aragón