What Are the Causes of High Glycine Levels?
High glycine levels, or hyperglycinemia, can result from several distinct scenarios, each presenting with its own set of symptoms and severity. Understanding the underlying cause is crucial for proper diagnosis and management.
Nonketotic Hyperglycinemia (NKH)
Nonketotic hyperglycinemia, also known as glycine encephalopathy, is a rare inherited metabolic disorder caused by a defect in the glycine cleavage enzyme system. This enzyme system is responsible for breaking down glycine, so a deficiency leads to an excessive buildup of the amino acid in the body, especially in the brain.
Symptoms of NKH often appear shortly after birth but can vary depending on the severity of the condition. There are two primary types:
- Severe NKH: Typically begins within days of birth with progressive lethargy, hypotonia (weak muscle tone), and feeding difficulties. This can rapidly progress to life-threatening breathing problems, seizures, and coma. Long-term survivors often face profound intellectual disability, spasticity, and difficult-to-control epilepsy.
- Attenuated NKH: Presents later in infancy or childhood with milder symptoms, which can include developmental delays, learning difficulties, hyperactivity, and milder seizures that are sometimes easier to treat. Some children may learn to walk and use sign language but often experience behavioral problems and may lose skills over time.
Acute Glycine Toxicity
Excessive glycine can be acutely absorbed in medical procedures, such as transurethral resection of the prostate (TURP) or hysteroscopic surgery, where large volumes of a glycine-based solution are used for irrigation. If this fluid is absorbed into the bloodstream, it can cause a condition known as TURP syndrome, with a distinct set of symptoms.
Key symptoms of acute glycine toxicity include:
- Visual disturbances, including transient blindness or colored vision (cyanopsia).
- Nausea and vomiting.
- Confusion and disorientation.
- Drowsiness or lethargy.
- Seizures and convulsions.
- Electrolyte imbalances, such as hyponatremia (low sodium).
- Hyperammonemia (excess ammonia), which further depresses consciousness.
Other Sources of High Glycine
Other less common factors can also lead to elevated glycine levels:
- Liver Failure: Severe liver failure can impair the body's ability to metabolize glycine, leading to a buildup.
- Medication Side Effects: Certain drugs, like the anticonvulsant valproate, are known to decrease the activity of the glycine cleavage enzyme system and increase glycine concentrations.
- Excessive Supplementation: While uncommon, consuming very large doses (more than 15-20 grams) of glycine supplements, especially without medical supervision, can lead to side effects such as gastrointestinal distress, drowsiness, and nausea.
Comparison of Glycine Toxicity: Acute Exposure vs. NKH
| Feature | Acute Glycine Toxicity (e.g., TURP Syndrome) | Nonketotic Hyperglycinemia (NKH) |
|---|---|---|
| Cause | Accidental absorption of glycine-based irrigating fluids during surgery. | Genetic defect in the glycine cleavage enzyme system. |
| Onset | Acute, during or immediately after a medical procedure. | Early infancy (neonatal) or later childhood, depending on the form. |
| Symptom Type | Visual disturbances, confusion, nausea, seizures, fluid shifts, hyperammonemia. | Developmental delay, seizures, hypotonia, spasticity, intellectual disability. |
| Visual Issues | Transient blindness is a hallmark sign. | Cortical blindness may occur in severe cases, but less prominently. |
| Prognosis | Symptoms typically resolve as excess glycine is cleared, often within 24 hours. | Severe NKH has a poor prognosis, while attenuated forms show variable outcomes. |
| Associated Condition | TURP syndrome | Genetic metabolic disorder |
How to Manage High Glycine Levels
Managing elevated glycine levels depends on the root cause. For genetic disorders like NKH, treatment often focuses on controlling symptoms and reducing glycine levels.
Management strategies include:
- Medication: Sodium benzoate or sodium phenylacetate can be used to help remove excess glycine from the body.
- Dietary Modifications: A low-protein diet may be recommended to limit glycine intake, although this alone is not sufficient due to the body's own glycine production.
- Ketogenic Diet: This specialized high-fat, low-carbohydrate diet has shown promise in reducing both plasma and brain glycine levels in some NKH patients, alongside other treatments for seizure control.
- Treating Acute Toxicity: In cases of acute glycine toxicity, treatment is supportive and focuses on correcting electrolyte imbalances, managing seizures, and waiting for the body to clear the excess glycine.
For mild side effects from supplements, simply reducing the dose or discontinuing use is usually sufficient.
Conclusion
The symptoms of too much glycine in the body range from mild gastrointestinal upset to severe, life-threatening neurological and developmental issues. Genetic conditions like Nonketotic Hyperglycinemia are a primary cause in infants, leading to severe developmental and neurological impairments. In adults, acute overdose can occur during certain medical procedures using glycine-based irrigation fluids, causing temporary but serious central nervous system and visual problems. Additionally, excessive glycine supplementation can cause mild side effects. Accurate diagnosis of the underlying cause is essential for effective treatment, which can range from supportive care and medication to dietary management and symptom control. For further reading on this rare metabolic disorder, a reliable resource is the National Institutes of Health (NIH).
