We see how children with mitochondrial diseases live, but how do they die?

Most current literature surrounding mitochondrial diseases in children focus on associated survival and clinical findings. Very few studies have looked at the factors surrounding death events and their causes. Eom et al. (2017) conducted a retrospective cohort study from patients in the Pediatrics Department at Gangnam Severance Hospital in Seoul, Korea examining risk factors for death in pediatric patients with mitochondrial diseases. The study population of 221 patients had confirmed mitochondrial disease diagnoses via clinical, histopathologic, enzymatic and metabolic parameters with a global mortality rate of 14% with a mean age of 6 years from 2006-2015. Of those who died, 48% were diagnosed with Leigh Syndrome, 45% were diagnosed with nonspecific mitochondrial disease, and 7% had MELAS syndrome. The top causes of death by prevalence were sepsis (55%), pneumonia (42%), DIC (29%), sudden unexpected death (29%) and ARDS (23%) with 1-3 causes of death identified per patient. Patient with early death (<6 yrs of age) were found to have more severe disease and die from more causes. Risk of death was associated with age of onset of disease symptoms. Limitations of this study, as noted in a subsequent letter to the editor, include lack of genetic confirmation of patients’ diagnoses as well as missing information regarding extensive family history, medications, diet, and history of epilepsy and cardiac and pulmonary involvement secondary to metabolic effects.

Mentee Comments

One of the conclusions of the study was that pediatric patients with mitochondrial disorders most commonly die from the same causes (i.e. sepsis, pneumonia) as the general pediatrics population. While these patients’ underlying mitochondrial disorder will result in impaired immunity (i.e. impaired respiratory effort) with increases risk of infections, close monitoring and surveillance to minimize this risk remains a feasible goal. Given the heterogeneous nature of mitochondrial disorders, it can be challenging to identify clinical manifestations and severity given the range of phenotypic variation in absence of confirmatory genetic testing. I think this is an important point for provider of these patients to remember when overall risk for death particularly when a specific diagnosis may remain elusive.

Jennifer Peralta, MD
Pediatric Resident, Children’s Hospital at Montefiore

Mentor Comments

We picked this article after a patient at our clinic with a mitochondrial disorder of unknown etiology was hospitalized with poor prognosis. It helped our team realize the importance of keeping children with mitochondrial disorders healthy, as once an illness alters the healthy state it can be hard for these children to recover. I agree with Dr. Peralta that caring for children without genetic confirmation can be challenging for providers but this study helps us remember that clinical presentation is almost as important if not more important than genetic testing some times.

Kristie Malik, MD
Complex Care, Children’s Hospital at Montefiore

Eom S, et al. Cause of Death in Children with Mitochondrial Diseases. Pedi Neuro. 2017 Jan, 66.