Introduction
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) is a mitochondrial disorder caused primarily by MT-TL1:m.3243A>G mutation variants, which typically presents in childhood or adolescence and can affect multiple organs systems, including the brain, heart, ears, eyes, kidneys, and GI tract. Known cardiac manifestations, such as arrhythmias and left ventricular hypertrophy, add complexity to MELAS management and prognosis. This case study explores the clinical course, genetic findings, and psychosocial challenges associated with a pediatric MELAS patient who died from a sudden cardiac event.

Case Presentation
 A 17-year-old male was referred for a hearing evaluation after a routine annual well-child check revealed reduced hearing in his right ear. Audiologic testing confirmed a diagnosis of bilateral high-frequency mild-to-moderate sensorineural hearing loss. Genetic testing related to hearing loss was performed and a pathogenic MT-TL1:m.3243A>G variant, with buccal heteroplasmy levels of 25-50%, was identified.

Diagnostic Workup
A cardiac evaluation was conducted soon after, which revealed mildly dilated right ventricle with preserved systolic function, normal left ventricular size and function, and no significant structural abnormalities. An electrocardiogram (ECG) showed sinus bradycardia without other abnormalities. The patient reported no cardiac symptoms, such as chest pain, palpitations, dizziness, or syncope, and remained physically active. At his genetics appointment, the patient and his family received comprehensive counseling on MELAS and its unpredictable phenotype. Routine labs, including thyroid function, lactic acid, creatinine, and liver function tests, and a metabolic urine study were ordered and returned normal results.

 

Treatment and Management
Given his initial lack of cardiac and neurological symptoms, the patient’s management plan primarily focused on routine surveillance for MELAS-related complications. The family discussed supplement options with the care team, including carnitine, creatinine, and coenzyme Q10. A follow up appointment was made to review urine sediment heteroplasmy levels once they were available.

Outcome and Follow-Up
Two-weeks after his genetics appointment, the patient experienced sudden cardiac arrest. His watch’s heart monitor recorded an abrupt heart rate cessation during sleep. Urine sediment results received after his death revealed heteroplasmy levels of 94%. The family was offered follow up genetic counseling to address any questions regarding the genetic findings and potential familial implications. Preliminary autopsy reports have identified the cause of death to be dilated cardiomyopathy. 

 

Discussion
This case illustrates the unpredictable and severe cardiac risks associated with MELAS, particularly in patients with MT-TL1:m.3243A>G variants, even in the absence of overt symptoms. The patient’s sudden death underscores the need for increased surveillance for MELAS patients, as well as the need for psychosocial support for families managing the emotional toll of this diagnosis. Sudden cardiac death, though rare, remains an under-recognized risk in this population and emphasizes the complex management challenges in mitochondrial disorders.

Conclusion
This case emphasizes the importance of routine cardiac monitoring for MELAS patients, regardless of symptom presentation. Genetics providers should remain aware of the potential cardiac risks and consider robust psychosocial interventions to support families managing this high-stakes and unpredictable disorder. Further research is essential to develop guidelines tailored to mitochondrial disorders. Additionally, increased awareness and standardized protocols for cardiac assessment could help identify at-risk patients and potentially mitigate the risk of sudden cardiac events in individuals with mitochondrial disease.