Researchers studied four children with a rare genetic condition that affects how their bodies use energy, called pyruvate dehydrogenase deficiency. This condition is caused by changes in a specific gene called PDHA1 and can cause serious brain problems starting in infancy. The study found that all four children had high levels of lactic acid in their blood and brain damage visible on scans. When doctors treated them with a special vitamin (thiamine) and a specific diet high in fats and low in carbohydrates (ketogenic diet), the children improved significantly. The researchers discovered a new genetic change that may cause this disease and learned more about how this rare condition affects children differently.
The Quick Take
- What they studied: How a rare genetic disease that damages the brain develops in children and whether special treatments can help them get better
- Who participated: Four children from Argentina with a rare genetic condition affecting how their bodies produce energy. Some had severe symptoms starting as newborns, while others developed problems more slowly during childhood.
- Key finding: All four children had the same type of genetic problem (in the PDHA1 gene) and showed similar signs like high acid levels in their blood and brain damage on scans. When treated with a vitamin and special diet, all four children improved with better seizure control and more stable health.
- What it means for you: If a baby or child shows signs of severe brain problems early in life or unusual neurological symptoms, doctors should consider testing for this rare genetic condition. Early diagnosis and treatment with thiamine and a ketogenic diet may help prevent serious complications. However, this is an extremely rare condition, so most families won’t encounter it.
The Research Details
This study examined four individual children with the same rare genetic disease in detail. The researchers collected information about each child’s symptoms, blood tests, brain scans, and genetic testing results. They also studied the specific genetic changes each child had to understand how these changes might affect the protein that helps the body use energy.
The doctors treated all four children with thiamine (a B vitamin) and put them on a ketogenic diet (a diet very high in fat and very low in carbohydrates). The researchers then tracked how well each child responded to this treatment over time, looking at whether seizures improved, whether the children developed normally, and whether their blood chemistry became more stable.
One of the genetic changes the researchers found had never been described before in medical literature. They used computer models to predict how this new genetic change might affect the protein’s ability to work properly.
This type of detailed case study is important for rare diseases because there aren’t many patients to study. By carefully documenting what happened with these four children—including their symptoms, test results, and how they responded to treatment—doctors can learn how to recognize this disease in other children and know what treatments might help. The discovery of a new genetic change also helps scientists understand the full range of ways this disease can develop.
This study is a detailed description of four real patients rather than a large controlled experiment, which means the findings are based on actual medical experience but can’t prove cause-and-effect as strongly as larger studies could. The strength of this work is that it provides detailed, real-world information about a very rare disease that affects only a handful of people worldwide. The researchers used multiple types of testing (genetic, blood tests, brain imaging) to confirm their findings, which makes the results more reliable. However, because only four patients were studied, these findings may not apply to every person with this condition.
What the Results Show
All four children had genetic changes in the PDHA1 gene, which is responsible for making a protein that helps cells produce energy. Three of the four children had a pattern of brain damage called Leigh syndrome, which is a serious neurological condition. All four children had high levels of lactic acid in their blood, which is a sign that their bodies weren’t using energy efficiently.
When the children were treated with thiamine (vitamin B1) and a ketogenic diet, all four showed significant improvement. The seizures that many of them experienced became much easier to control with medication. The children’s overall brain development and function improved, and their blood chemistry became more stable over time.
The researchers identified four different genetic changes in the PDHA1 gene among the four children. One of these changes had never been reported before. This new genetic change appears to affect how well the protein can bind to a helper molecule called thiamine pyrophosphate, which is essential for the protein to work correctly.
The study found that this rare disease can show up in very different ways in different children. Some children had severe, life-threatening symptoms starting as newborns (including breathing problems), while others developed symptoms more slowly during early childhood. Despite these differences in how the disease started, all children showed similar patterns on brain scans and in their blood tests. The brain imaging revealed structural abnormalities in specific areas of the brain, particularly in regions that control movement and coordination. One child showed a previously undescribed pattern of brain damage that the researchers documented for the first time.
This research adds to what scientists already know about pyruvate dehydrogenase deficiency by identifying a new genetic change and describing how it might affect the protein’s function. Previous research has shown that thiamine and ketogenic diet can help some patients with this condition, and this study confirms those findings in these four Argentine children. The discovery of the new genetic variant expands the known spectrum of genetic changes that can cause this disease. The study also documents a new pattern of brain damage that hadn’t been clearly described before, which helps doctors recognize the disease in other patients.
This study describes only four children, so the findings may not apply to all people with this rare genetic condition. Because there are so few patients with this disease worldwide, it’s difficult to do larger studies. The study doesn’t include a comparison group of children without the disease, so we can’t be completely certain that all the symptoms are caused by the genetic changes (though the evidence strongly suggests they are). The children were followed for different lengths of time, so we don’t know how they’ll do in the very long term. The study was done in Argentina, so the findings may not apply to people from different genetic backgrounds.
The Bottom Line
For families with a child showing severe unexplained brain problems in infancy or unusual progressive neurological symptoms: Ask your doctor about genetic testing for pyruvate dehydrogenase deficiency if other common causes have been ruled out. If diagnosed, treatment with thiamine supplementation and a ketogenic diet appears to help based on this research (moderate confidence level). Work with a metabolic specialist or neurologist experienced with rare genetic diseases. Regular monitoring of blood acid levels and neurological function is important. These recommendations are based on a small study of four patients, so discuss individual treatment plans with your medical team.
Parents and doctors caring for infants or young children with unexplained severe brain damage, seizures, or progressive neurological problems should be aware of this condition. Genetic counselors and metabolic specialists should consider this diagnosis in their differential diagnosis. This is an extremely rare condition, so most families won’t be affected, but early recognition can be life-changing for the few families who do have it.
Based on this study, children who received treatment showed improvements in seizure control within weeks to months. Improvements in overall neurological function and metabolic stability appeared to develop over months to years. However, this is a serious condition, and long-term outcomes vary. Some children showed significant improvement while others had more limited gains. It’s important to have realistic expectations and work closely with medical specialists.
Want to Apply This Research?
- If a child has been diagnosed with this condition, track seizure frequency and duration (number of seizures per week and how long each lasts), blood lactate levels from regular lab work, and developmental milestones achieved. Record any changes after starting treatment with thiamine and ketogenic diet.
- For families managing this condition: Use the app to set reminders for thiamine supplementation at the same time each day. Track adherence to the ketogenic diet by logging meals. Monitor and record seizure activity to share with doctors at appointments. Set reminders for scheduled blood tests to monitor lactic acid levels.
- Create a long-term tracking dashboard that shows trends in seizure frequency over months, records of blood test results from clinic visits, notes on developmental progress, and medication effectiveness. Share this data with your medical team regularly to help them adjust treatment as needed. Track any new symptoms or concerns that develop over time.
This research describes a very rare genetic condition affecting only a small number of children worldwide. The findings are based on detailed study of four patients and should not be used for self-diagnosis. If you suspect your child has symptoms of a rare neurological or metabolic disorder, consult with a qualified pediatric neurologist or metabolic specialist for proper evaluation and diagnosis. Treatment decisions should always be made in consultation with your medical team. This information is educational and does not replace professional medical advice, diagnosis, or treatment.