Researchers studied 18 babies with a serious seizure condition called infantile epileptic spasms syndrome caused by changes in mitochondrial genes—the parts of cells that produce energy. They found that most babies with these gene changes had seizures that didn’t respond well to medications and had poor outcomes. The study identified 12 different genes involved and found that high lactate levels in the blood, along with brain shrinkage on imaging, could help doctors diagnose this condition earlier. While the findings are concerning, they help doctors better understand and potentially recognize this rare condition in other children.

The Quick Take

  • What they studied: How changes in genes that control cell energy production cause severe seizures in babies, and what signs doctors should look for to diagnose it
  • Who participated: 18 babies (11 boys and 7 girls) who had severe seizures starting around 6 months old due to mitochondrial gene changes, treated at one hospital in China between 2016 and 2025
  • Key finding: Most babies (14 out of 18) had seizures that didn’t stop even with multiple medications, and only 1 out of 12 older children had good long-term outcomes. High lactate levels and brain shrinkage on brain scans were common warning signs.
  • What it means for you: If your baby has unexplained seizures starting around 6 months old, doctors should consider testing for mitochondrial gene changes, especially if seizures don’t respond to standard treatments. This is a rare condition, but early recognition may help with management.

The Research Details

This was a case-series study, meaning doctors reviewed medical records of 18 babies who all had the same rare condition caused by mitochondrial gene changes. They looked at when seizures started, what symptoms appeared, blood test results, brain imaging findings, and how well different treatments worked. The babies were followed for an average of 3 years to see how they did over time.

The researchers examined genetic testing results to identify which specific genes were changed in each baby. They also looked at brain imaging scans (MRI) to see if there were visible changes in the brain structure. Blood tests measured lactate levels, which can be elevated when mitochondria aren’t working properly.

This research approach is important because infantile epileptic spasms syndrome caused by mitochondrial gene changes is very rare, so studying multiple cases together helps doctors recognize patterns. By documenting what these babies looked like, what tests showed abnormalities, and how they responded to treatment, doctors can better identify other children with this condition and understand what to expect.

This study has some important limitations to understand: it’s a small group of only 18 babies from one hospital, so the findings may not apply to all babies with this condition worldwide. It’s a descriptive study that documents what happened rather than comparing different treatments directly. The researchers didn’t have a control group of healthy babies to compare against. However, the detailed genetic testing and systematic documentation of clinical features provide valuable information about this rare condition.

What the Results Show

The study found that 12 different mitochondrial genes were responsible for seizures in these 18 babies. The most common gene involved was AFG3L2 (found in 4 babies), followed by PARS2 (3 babies). These genes are involved in either producing energy in cells or making proteins that cells need to function.

Most babies (14 out of 18) had seizures that didn’t respond to standard seizure medications, even when doctors tried two or more different drugs. This is called drug-resistant epilepsy and is a serious problem. Only 5 babies had their seizures controlled for at least 28 days with ACTH or prednisone (strong anti-inflammatory medications), and even then, most still needed additional seizure medications.

Brain imaging showed that 10 babies had brain shrinkage, and 3 babies had damage in specific brain areas (basal ganglia, thalamus, or midbrain). Seven babies had elevated lactate levels in their blood, which suggests their cells weren’t producing energy properly. Sadly, 3 babies died during the follow-up period, and among the 12 babies who were at least 3 years old at last check-up, only 1 had good long-term outcomes.

The ketogenic diet (a high-fat, low-carbohydrate diet sometimes used for seizures) was tried in 4 babies and helped only 1 baby—the one with a PDHA1 gene change. This suggests that the ketogenic diet may be worth trying in specific types of mitochondrial gene changes. The study also found that seizures typically started around 6 months of age, which is an important clue for doctors. The combination of high lactate levels plus brain shrinkage or specific brain lesions appeared in multiple babies, suggesting this pattern could help doctors diagnose this condition.

Previous research has shown that mitochondrial disorders can cause seizures, but this study provides specific information about how these gene changes present in babies with infantile epileptic spasms syndrome. The poor response to medications and poor long-term outcomes match what other researchers have found with mitochondrial-related seizure disorders. The genes identified in this study (particularly AFG3L2 and PARS2) have been reported in other mitochondrial disease cases, confirming these are important genes to test for.

The main limitation is the small sample size of only 18 babies from one hospital in China, so these findings may not represent all babies worldwide with this condition. The study didn’t compare different treatment approaches directly, so it’s hard to say which treatments work best. There was no control group of healthy babies for comparison. The follow-up time varied between babies (ranging from 1.5 to 4.3 years), so some babies weren’t followed as long as others. The study is descriptive rather than experimental, meaning it documents what happened but doesn’t prove cause-and-effect relationships. Additionally, genetic testing methods may have improved over the 9-year study period, potentially affecting which gene changes were detected.

The Bottom Line

If your baby develops seizures around 6 months of age that don’t respond well to standard seizure medications, ask your doctor about testing for mitochondrial gene changes. Blood tests showing high lactate levels combined with brain imaging showing shrinkage or specific lesions should raise suspicion for this condition. While there’s no cure for mitochondrial gene changes, early diagnosis helps doctors manage seizures more effectively and prepare families for the likely course of the illness. The ketogenic diet may be worth trying, especially if your baby has certain gene changes like PDHA1.

Parents and doctors should care about this research if a baby has unexplained seizures starting around 6 months old, especially if seizures don’t respond to standard medications. Genetic counselors and pediatric neurologists should be aware of these gene changes when evaluating babies with difficult-to-treat seizures. This research is less relevant for babies with seizures that start at different ages or that respond well to standard treatments. Families with known mitochondrial disorders should discuss seizure risk with their doctors.

Seizures typically start around 6 months of age and often become apparent within the first year. Most babies show signs of drug-resistant epilepsy within the first few months of seizure onset. Long-term outcomes become clearer by age 3 years, when most children in this study showed significant developmental delays or poor outcomes. Families should expect this to be a long-term condition requiring ongoing management rather than something that resolves quickly.

Want to Apply This Research?

  • Track seizure frequency and type daily (number of spasm episodes, duration, time of day), medication doses and timing, and any changes in alertness or development. Note any patterns related to illness, sleep, or other factors.
  • Work with your neurologist to maintain a detailed seizure diary in the app, recording each seizure episode with date, time, duration, and any triggers noticed. This helps doctors adjust medications and identify patterns. Also track medication adherence to ensure doses aren’t missed.
  • Use the app to monitor seizure control over weeks and months, tracking whether seizures are increasing, decreasing, or staying the same. Document any side effects from medications. Share monthly summaries with your doctor to guide treatment decisions. Track developmental milestones to monitor overall progress.

This research describes a rare medical condition affecting babies. If your child has seizures or you suspect a mitochondrial disorder, consult with a pediatric neurologist or geneticist for proper evaluation and diagnosis. This information is educational and should not replace professional medical advice. Genetic testing and treatment decisions should only be made with qualified healthcare providers. The prognosis described in this study is specific to these 18 cases and may not apply to all children with mitochondrial gene changes. Always discuss your child’s individual situation, test results, and treatment options with your medical team.