Summary about Disease
Glycine encephalopathy (GE), also known as nonketotic hyperglycinemia (NKH), is a rare, inherited metabolic disorder that affects the brain and nervous system. It is characterized by a deficiency in the enzyme system that breaks down glycine, an amino acid. This deficiency leads to an accumulation of glycine in the body, especially in the brain, causing severe neurological problems. GE presents in varying degrees of severity, with some individuals experiencing profound developmental delays and seizures from birth, while others have a milder, later-onset form.
Symptoms
Symptoms vary in severity, but can include:
Severe form (neonatal): Hypotonia (floppy muscle tone), lethargy, seizures (often myoclonic), apnea (pauses in breathing), developmental delays, intellectual disability, abnormal movements, hiccups, coma.
Attenuated (milder) form: Hypotonia, developmental delays (may be less severe), intellectual disability, seizures (may be present or absent), behavioral problems, hyperactivity, spasticity.
Late-onset form: Progressive spastic paraparesis (muscle weakness and stiffness in the legs), optic atrophy (damage to the optic nerve), intellectual disability.
Causes
Glycine encephalopathy is caused by mutations in genes involved in the glycine cleavage system (GCS). The most common genes affected are GLDC and *AMT*. These genes provide instructions for making proteins that are part of the GCS enzyme complex, which is responsible for breaking down glycine. Mutations in these genes disrupt the function of the GCS, leading to a buildup of glycine. GE is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
4. Medicine used There is no cure for glycine encephalopathy, and treatment focuses on managing symptoms. Medications used may include:
Sodium benzoate: Helps to reduce glycine levels in the blood and brain by converting glycine to hippuric acid, which is then excreted in the urine.
Dextromethorphan: An NMDA receptor antagonist that may help reduce seizure frequency.
Diazepam or other benzodiazepines: Used to control seizures.
Anti-epileptic drugs (AEDs): May be used if other medications do not control seizures.
Supportive therapies: Physical therapy, occupational therapy, speech therapy, and nutritional support.
Is Communicable
No, glycine encephalopathy is not communicable. It is a genetic disorder caused by mutations in genes, not by an infectious agent.
Precautions
Since GE is a genetic disorder, prevention is not possible in affected individuals. However, genetic counseling is recommended for families with a history of GE who are planning to have children. Genetic testing can determine if parents are carriers of the mutated genes. For individuals with GE, precautions focus on managing their symptoms and preventing complications. This may include:
Following a prescribed medication regimen to control seizures and reduce glycine levels.
Maintaining a healthy diet and ensuring adequate hydration.
Avoiding activities that may trigger seizures.
Working closely with a team of healthcare professionals, including a neurologist, geneticist, and therapists.
Monitoring for signs of respiratory distress and seeking prompt medical attention if necessary.
How long does an outbreak last?
Glycine encephalopathy is not an infectious disease with outbreaks. It is a chronic, lifelong condition. Symptoms may fluctuate in severity over time, but the underlying genetic defect persists.
How is it diagnosed?
Diagnosis of glycine encephalopathy typically involves:
Clinical evaluation: Assessment of the individual's symptoms and medical history.
Blood and cerebrospinal fluid (CSF) glycine levels: Elevated glycine levels in both blood and CSF are characteristic of GE. The CSF/plasma glycine ratio is typically elevated.
Genetic testing: To identify mutations in the GLDC and *AMT* genes.
MRI of the brain: May show characteristic abnormalities, such as white matter changes.
EEG (electroencephalogram): To evaluate brain activity and detect seizures.
Timeline of Symptoms
9. Timeline of symptoms The timeline of symptoms varies depending on the severity of the condition:
Neonatal form: Symptoms typically appear within the first few days of life, often including hypotonia, lethargy, seizures, and apnea.
Attenuated form: Symptoms may be present at birth but are less severe, or they may develop later in infancy or early childhood. Developmental delays and intellectual disability are common.
Late-onset form: Symptoms may not appear until later in childhood or adulthood. Progressive spastic paraparesis and optic atrophy are characteristic.
Important Considerations
Early diagnosis and treatment are crucial to minimize brain damage and improve outcomes.
Management of glycine encephalopathy requires a multidisciplinary approach, involving neurologists, geneticists, therapists, and other healthcare professionals.
Genetic counseling is important for families affected by GE.
Research is ongoing to develop new and more effective treatments for GE.
Support groups and advocacy organizations can provide valuable resources and support for individuals with GE and their families.