Cardiac Risks in Patients with AHC: What Should We Know?

Alternating Hemiplegia of Childhood (AHC) is a rare neurological disorder, affecting approximately 1 in 1,000,000 children, caused by mutations in the ATP1A3 gene. While AHC primarily manifests with neurological symptoms—paralysis, dystonic movements, seizures, etc.—research indicates that these patients also have an increased risk of sudden cardiac death.

In 2025, an international study published in JAMA Pediatrics confirmed a direct link between ATP1A3 mutations and cardiac arrhythmias in patients with AHC. This article summarizes the facts and provides guidance for parents and physicians.

What is ATP1A3?

ATP1A3 is a gene that encodes part of the sodium-potassium pump—an essential protein for brain function. Mutations in this gene lead to AHC, causing episodes of paralysis, seizures, involuntary movements, and other neurological disorders.

Recent discoveries show that some of these mutations—especially D801N—can also affect the electrical activity of the heart, increasing the risk of life-threatening arrhythmias.

What is Short QT Syndrome?

The QT interval on an electrocardiogram (ECG) measures the time it takes for the heart to "recharge" between beats. In Short QT Syndrome (SQTS) this period is too short, increasing the risk of dangerous heart rhythm disturbances and sudden cardiac arrest.

A QT interval, corrected for heart rate (QTc), is considered pathologically short when it is below 350 ms.

What Do the Results Show?

A large international study analyzed 148 AHC patients and compared them with healthy individuals to better understand the cardiac risks associated with ATP1A3 mutations. The findings are significant:

1. Shortened QT Interval in Patients with ATP1A3 Mutations

• Children with ATP1A3 mutations, especially D801N, have a significantly shorter QT interval than healthy peers.
• 69% of patients with D801N had a QTc below 370 ms.

2. D801N Is the Highest-Risk Mutation

• This mutation leads to a mean QTc of 381.8 ms.
• In comparison, the E815K mutation results in a QTc of 393.6 ms.
• QTc < 370 ms was found in 69% of D801N carriers, but only in 19% of those with E815K.

3. Only D801N Patients Survived Cardiac Arrest

• Three patients with D801N experienced serious cardiac events—including arrhythmias and cardiac arrest.
• No such events were observed with any other mutations.

4. Laboratory Evidence

• Lab-grown cardiac cells derived from D801N carriers showed irregular electrical activity, confirming a predisposition to arrhythmias.

What Does This Mean for Families?

• Regular cardiac checkups are essential.
  • ECGs should be part of routine monitoring.
  • If a short QT is detected, additional testing is needed.
• Inform doctors before any sedation or anesthesia.
  • Some medications used during procedures can slow the heart rate, increasing the risk of dangerous arrhythmias.
  • Discuss the safest approach with your child's medical team.

• Watch for symptoms of heart rhythm disturbances.

  • Fainting, dizziness, or unexplained seizures may be warning signs of a cardiac issue.

  • Seek medical attention immediately if such symptoms occur.

• Some patients may need extra protection.

  • High-risk cases may require an implantable defibrillator (ICD) to prevent sudden cardiac arrest.

Next Steps for Families

If your child or a family member has AHC or an ATP1A3-related condition, consider the following:

• Talk to your doctor about doing an ECG to assess cardiac risk.
• Share this information with your child’s medical team to ensure they are aware of the latest research.
• Be prepared for medical procedures by discussing the safest anesthesia and medication options.
• Stay updated on new studies and recommendations related to ATP1A3 conditions.

Final Thoughts

This study underscores that heart health should be an integral part of caring for patients with ATP1A3-related disorders. Although these conditions are primarily known for their neurological impact, the research shows that some individuals may also face elevated cardiac risks.

With awareness and collaboration with the medical team, you can take proactive steps to monitor and protect your loved one’s heart health.

For more information, consult a pediatric cardiologist or an electrophysiologist specializing in heart rhythm disorders.