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PubMed This is a summary of 23 peer-reviewed journal articles Updated
Neurology

Symptoms and Emergency Warning Signs

At a Glance

SANDO symptoms such as imbalance, numbness, slurred speech, eye-movement weakness, and fatigue may develop gradually, but seizures, sudden neurological changes, liver failure signs, or breathing problems require immediate emergency care; valproate should be avoided in POLG-related disease.

Living with SANDO syndrome means navigating a combination of daily physical challenges and knowing when a new symptom requires immediate medical action. Because SANDO is part of a group of conditions caused by mutations in the POLG gene, your body handles certain medications and metabolic stresses differently than most people [1][2].

Daily Symptoms and Routine Management

The symptoms of SANDO often develop slowly over years. While they can be frustrating or limiting, they are generally considered “routine” for the condition rather than emergencies [3].

  • Sensory Ataxia (Imbalance): You may feel unsteady on your feet or “clumsy.” This happens because the nerves that tell your brain where your limbs are located are not working correctly [4]. This imbalance often feels worse in the dark or on uneven surfaces [3].
  • Neuropathy (Numbness/Tingling): Damage to the peripheral nerves can cause “pins and needles,” numbness, or pain in your hands and feet [4].
  • Dysarthria and Dysphagia: You may notice your speech is slurred or that you have difficulty swallowing (dysphagia) [5][6].
  • Eye Changes: Weakness in the eye muscles (ophthalmoparesis) can limit how far you can look in any direction, and you may develop drooping eyelids (ptosis) [3][7].
  • Fatigue and Muscle Weakness: Many patients experience profound tiredness or muscle aching after physical activity [8][9].

THE CRITICAL WARNING: Valproate Danger

If you have known or suspected SANDO or any POLG-related disorder, there is one medication you must never take: Valproic acid (also known as valproate, sodium valproate, divalproex, Depakote, or Epilim) [10][11].

In patients with POLG mutations, valproate carries a high risk of causing sudden, severe, and potentially fatal liver failure [11][12]. The drug interferes with the already-struggling mitochondria in your liver cells, leading to rapid cell death [13]. A systematic review found a very high mortality rate (over 50%) in valproate-exposed patients who had recessive POLG disease [11].

Action Item: Ensure that a serious medication contraindication alert—“DO NOT USE: known POLG disease, risk of fatal liver injury”—is listed in your medical records and on any medical alert jewelry you wear. This is a severe drug warning, not a typical immune allergy. If you are prescribed a new medication for seizures or migraines, double-check with your neurologist to ensure it is not a form of valproate [10]. Do not abruptly stop any current antiseizure medication without medical guidance.

Emergency Warning Signs (Call Local Emergency Number)

Certain symptoms in SANDO are not part of the normal progression and require immediate hospital evaluation. While severe complications like acute liver failure or stroke-like episodes are more characteristic of severe POLG phenotypes (like Alpers-Huttenlocher syndrome), they remain possible red flags in SANDO [14][15].

1. Seizures and Status Epilepticus

Seizures in POLG-related disease can start suddenly.

  • Warning: A first-time seizure, any seizure lasting more than 5 minutes, or multiple seizures where you do not fully “wake up” in between, is a medical emergency called status epilepticus [16].
  • Urgency: This requires aggressive emergency treatment by a clinician with individualized non-valproate medications to prevent brain injury [17][18].
  • Seizure First Aid: Family members should time the seizure, place you on your side if safe, protect your head from injury, avoid restraining you, and never put anything in your mouth.

2. Stroke-Like Episodes and Sudden Neurological Changes

  • Warning: Sudden new confusion, a severe new headache with vomiting, sudden loss of vision, or sudden new weakness on one side of the body [17][19].
  • Urgency: Call your local emergency number immediately. Do not wait to see a mitochondrial specialist. These symptoms require the standard emergency stroke pathway to evaluate for both conventional ischemic strokes and POLG stroke-like episodes [20][17].

3. Acute Liver Failure

This can happen even without valproate exposure [1].

  • Warning: Yellowing of the skin or eyes (jaundice), unusual bleeding or bruising, extreme sleepiness (lethargy), or sudden swelling in the abdomen [12][21].
  • Urgency: This requires immediate blood tests for liver enzymes, ammonia levels, and blood clotting ability [22][21].

4. Respiratory Crisis

  • Warning: Difficulty breathing, blue-tinted lips, or severe choking/inability to clear secretions while eating [23][6].
  • Urgency: This may indicate severe swallowing muscle weakness or respiratory failure [6].

Summary of Action Levels

Action Level Symptoms
Emergency (Call emergency number/Go to ED) First seizure; seizure >5 mins; sudden confusion or focal weakness; sudden vision loss; jaundice; breathing difficulty; severe headache with vomiting.
Urgent (Same-Day Doctor Review) Coughing when drinking fluids; sudden inability to tolerate foods.
Routine (Next Appointment) Gradual changes in speech; slowly worsening eyelid droop; persistent mild fatigue or numbness.

Common questions in this guide

Which SANDO symptoms are routine, and which need emergency care?
Gradual imbalance, numbness or tingling, slurred speech, eyelid drooping, eye-movement problems, swallowing difficulty, and fatigue can occur as part of SANDO. A first seizure, a seizure lasting more than five minutes, sudden confusion or weakness, sudden vision loss, jaundice, severe headache with vomiting, or breathing difficulty needs immediate emergency evaluation.
Why is valproate unsafe for people with SANDO?
POLG-related disease can make valproate medicines—including valproic acid, sodium valproate, divalproex, Depakote, and Epilim—cause sudden, severe, and potentially fatal liver injury. Make sure this contraindication is in your medical record and tell every clinician; do not stop an antiseizure medicine abruptly without medical guidance.
When should I call emergency services for a seizure or sudden neurologic change?
Call your local emergency number for a first seizure, a seizure lasting longer than five minutes, repeated seizures without full recovery, sudden confusion, new one-sided weakness, sudden loss of vision, or a severe new headache with vomiting. These symptoms need prompt evaluation for both common emergencies and POLG-related complications.
What should my family do if I have a seizure?
They should time the seizure, protect your head, place you on your side when it is safe, avoid restraining you, and never put anything in your mouth. They should call emergency services for a first seizure, a seizure lasting more than five minutes, or repeated seizures when you do not fully wake between them.
What are the warning signs of acute liver failure in SANDO?
Yellow skin or eyes, unusual bleeding or bruising, extreme sleepiness, and sudden abdominal swelling can signal acute liver failure. Seek immediate hospital care, because clinicians may need to check liver enzymes, ammonia, and blood-clotting tests; this complication can occur even without valproate exposure.
When are swallowing or breathing problems an emergency?
Severe difficulty breathing, blue-tinted lips, or choking and inability to clear secretions are emergencies and require immediate help. Coughing when drinking or a sudden inability to tolerate food should receive same-day medical review because swallowing weakness can worsen.

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References

References (23)
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This page is for informational purposes only and does not constitute medical advice. Discuss your SANDO emergency plan and medication safety with your neurologist, and call your local emergency number for severe or sudden symptoms.

Guide contents Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome
Research & Literature
01 Understanding SANDO Syndrome 03 Diagnosis, POLG Genetics, and Look-Alikes