Non-ketotic Hyperglycinemia
Disease Details
Family Health Simplified
- Description
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Non-ketotic hyperglycinemia is a rare genetic disorder characterized by an accumulation of glycine in the body, leading to severe neurological symptoms.
One-sentence description: Non-ketotic hyperglycinemia is a genetic disorder that results in high levels of glycine in the brain and other tissues, causing severe neurological impairments. - Type
- Non-ketotic hyperglycinemia is an autosomal recessive disorder. This means that an affected individual must inherit two copies of the defective gene, one from each parent, to exhibit symptoms of the condition.
- Signs And Symptoms
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Non-ketotic hyperglycinemia (NKH) is a rare genetic disorder characterized by an accumulation of glycine in the body.
Signs and Symptoms:
- Lethargy
- Poor feeding
- Hypotonia (low muscle tone)
- Apnea (periods of stopped breathing)
- Seizures
- Developmental delay
- Intellectual disability
- Spasticity (muscle stiffness)
- Progressive neurological deficits
Nan: Not applicable in this context. - Prognosis
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Non-ketotic hyperglycinemia (NKH) is a rare, genetic metabolic disorder characterized by an accumulation of glycine in the body. The prognosis for individuals with NKH varies based on the severity of the condition.
**Prognosis:**
1. **Severe Neonatal Form:** This is the most common and most severe form. Affected infants typically present with profound lethargy, hypotonia, and often develop seizures and apnea shortly after birth. The prognosis is generally poor, with a high risk of early mortality. Survivors usually experience significant neurological impairment, including intellectual disability and seizures.
2. **Attenuated Forms:** These less severe forms can present later in infancy or childhood. Affected individuals may exhibit developmental delays, mild to moderate intellectual disability, and less frequent or milder seizures. The prognosis is better compared to the severe neonatal form, but affected individuals still face significant challenges and require lifelong care and management.
Management and treatment focus on supportive care, controlling seizures, and optimizing developmental outcomes, but there is currently no cure for NKH. - Onset
- Non-ketotic hyperglycinemia (NKH) typically presents in the neonatal period, often within the first few days or weeks of life. Symptoms include lethargy, poor feeding, hypotonia (low muscle tone), seizures, and developmental delay.
- Prevalence
- Non-ketotic hyperglycinemia (NKH) is an extremely rare metabolic disorder. The estimated prevalence is approximately 1 in 60,000 newborns, although this can vary slightly depending on the population studied.
- Epidemiology
- Non-ketotic hyperglycinemia (NKH) is a rare inherited metabolic disorder. Its global prevalence is estimated to be between 1 in 60,000 to 1 in 250,000 live births, but exact numbers can vary due to underreporting and population differences. The condition is more commonly observed in families where consanguineous marriages are prevalent.
- Intractability
- Non-ketotic hyperglycinemia (NKH) is generally considered an intractable disease. This means it is difficult to manage or cure due to its genetic and metabolic nature. Current treatments focus on managing symptoms and improving quality of life, but there is no definitive cure. Treatment options may include medications to reduce glycine levels and supportive therapies to address developmental and neurological issues.
- Disease Severity
- Non-ketotic hyperglycinemia (NKH) is a severe metabolic disorder characterized by an accumulation of glycine in the body. Disease severity can be variable but often includes profound neurological impairments, developmental delays, seizures, and hypotonia. The majority of affected individuals may experience severe symptoms leading to significant morbidity and mortality, particularly in classic infantile-onset cases.
- Pathophysiology
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Non-ketotic hyperglycinemia (NKH) is a rare genetic disorder caused by a defect in the glycine cleavage system. This system is responsible for breaking down the amino acid glycine. In NKH, the activity of the glycine cleavage system is significantly reduced or absent, leading to an accumulation of glycine in the body, particularly in the central nervous system.
The excess glycine in the brain interferes with normal neurological function, resulting in various neurological symptoms. The elevated glycine levels can disrupt neurotransmitter balance and can be excitotoxic, causing damage to neurons and impairing brain development and function.
Symptoms of NKH typically present in the neonatal period and can include hypotonia (low muscle tone), seizures, apnea (brief episodes of not breathing), and developmental delay. Without effective treatment, the prognosis is generally poor, with affected individuals experiencing severe neurological impairment and high morbidity. - Carrier Status
- Non-ketotic hyperglycinemia is an autosomal recessive disorder. Carrier status means that a person has one mutated copy of the gene responsible for the condition but does not exhibit symptoms. Testing for carrier status can involve genetic screening to identify mutations in the GLDC, AMT, or GCSH genes, which are associated with this disorder.
- Mechanism
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Non-ketotic hyperglycinemia (NKH) is a rare genetic disorder characterized by an accumulation of glycine in bodily tissues and fluids, due to a defect in the glycine cleavage system. The primary mechanism involves a deficit in one or more of the enzymes within this system, impairing glycine breakdown.
**Molecular Mechanisms:**
1. **Enzyme Deficiency:** The glycine cleavage system comprises four core components: P-protein (glycine decarboxylase), T-protein (aminomethyltransferase), H-protein (a lipoate-bearing protein), and L-protein (dihydrolipoamide dehydrogenase). Mutations in the genes encoding these proteins, particularly in the GLDC (for P-protein) and AMT (for T-protein), are often responsible for NKH.
2. **Genetic Mutations:** Mutations in the GLDC gene are most common and result in deficient or defective P-protein, which plays a crucial role in glycine decarboxylation. This enzyme catalyzes the initial step of glycine cleavage, converting glycine into carbon dioxide and transferring the methylamine moiety to the T-protein.
3. **Accumulation of Glycine:** As a result of these enzymatic defects, glycine cannot be adequately processed and accumulates in the blood, cerebrospinal fluid, and tissues, especially in the central nervous system. Elevated glycine levels disrupt normal neurotransmission due to its role as a neurotransmitter and NMDA receptor co-agonist, leading to various neurological symptoms.
Understanding these molecular mechanisms underscores the pathophysiology of NKH, highlighting the importance of early diagnosis and potential intervention strategies. - Treatment
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Non-ketotic hyperglycinemia (NKH) is treated primarily through dietary management and medications. Treatments include:
1. **Medications:**
- **Sodium Benzoate:** Helps reduce glycine levels.
- **Dextromethorphan:** May reduce symptoms by blocking NMDA receptors affected by high glycine levels.
- **Antiseizure medications:** Manage epilepsy symptoms often associated with NKH.
2. **Dietary Management:**
- **Low-protein diet:** Aims to manage glycine levels in the body.
3. **Supportive Therapies:**
- Physical therapy and specialized educational support for developmental issues.
These treatments are mainly supportive and aim to manage symptoms, as there is currently no cure for NKH. - Compassionate Use Treatment
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Non-ketotic hyperglycinemia (NKH) is a rare, inherited metabolic disorder characterized by an accumulation of glycine in the body. Treatment options are limited and primarily aim to manage symptoms rather than cure the condition.
For compassionate use treatment or off-label/experimental treatments, the following approaches have been considered:
1. **Sodium benzoate**: This compound can help reduce glycine levels in the body by promoting its excretion through the urine. While not a cure, it may alleviate some symptoms and is often used off-label in the treatment of NKH.
2. **Dextromethorphan**: Known for its use as a cough suppressant, dextromethorphan acts as an NMDA receptor antagonist. It may help reduce neurological symptoms by blocking the effects of elevated glycine in the brain.
3. **Ketogenic diet**: Some reports suggest that a ketogenic diet, which is high in fats and low in carbohydrates, may benefit patients by altering the brain's metabolism. However, its effectiveness varies and should be monitored closely by healthcare professionals.
4. **Experimental therapies**: Ongoing research into gene therapy and enzyme replacement therapy is exploring potential long-term treatments. These are experimental and not yet widely available but show promise for the future.
Consultation with a specialist familiar with NKH is crucial for determining the most appropriate treatment and for considering participation in clinical trials, if applicable. - Lifestyle Recommendations
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Non-ketotic hyperglycinemia (NKH) is a rare genetic disorder that leads to an accumulation of the amino acid glycine in the body. Lifestyle recommendations for managing NKH typically focus on supportive care and symptom management rather than lifestyle changes alone. Here are some general recommendations:
1. **Regular Medical Follow-ups:** Frequent visits to a specialist who is knowledgeable about NKH for monitoring and managing complications.
2. **Dietary Management:** While specific dietary interventions are still under investigation, it is important to follow any nutritional guidelines provided by a healthcare professional.
3. **Medications:** Adherence to prescribed medications such as sodium benzoate and dextromethorphan, which can help reduce glycine levels and manage symptoms.
4. **Therapies:** Involvement in physical, occupational, and speech therapy as recommended to improve motor skills and communication abilities.
5. **Seizure Management:** If seizures are present, following an epilepsy management plan created by a neurologist.
6. **Support Systems:** Engaging with support groups and networks for families dealing with NKH for emotional support and practical advice.
Each patient with NKH may require a tailored approach based on the severity and specific symptoms they experience. - Medication
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Non-ketotic hyperglycinemia (NKH) is a genetic disorder characterized by an excess of glycine in the body due to a defect in the glycine cleavage system. Treatment primarily focuses on managing symptoms and improving quality of life. Currently, there is no cure. Medications used typically include:
1. **Sodium Benzoate**: Helps to reduce glycine levels.
2. **Dextromethorphan**: Used to inhibit NMDA receptors and reduce neurological symptoms.
3. **Ketamine**: Also used to inhibit the NMDA receptor in severe cases.
4. **Anticonvulsants**: Used for seizure control, as seizures are common in NKH.
Early intervention with these medications can help manage some of the symptoms associated with NKH. Nonetheless, the effectiveness of treatment can vary among individuals. - Repurposable Drugs
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Non-ketotic hyperglycinemia (NKH) is a rare inherited metabolic disorder characterized by an accumulation of glycine in the body due to a defect in the glycine cleavage system. Currently, there is no curative treatment for NKH, and management is primarily supportive. However, some drugs have been repurposed to manage symptoms. These include:
1. **Sodium Benzoate**: Helps to reduce glycine levels by conjugating with glycine to form hippurate, which is excreted in the urine.
2. **Dextromethorphan**: Acts as an NMDA receptor antagonist and may help to reduce some neurological symptoms by inhibiting excitatory neurotransmission.
3. **Ketamine**: Another NMDA receptor antagonist used experimentally to help manage seizures and other neurological symptoms.
These medications can help manage some symptoms but do not address the underlying cause of the disorder. - Metabolites
- In non-ketotic hyperglycinemia (NKH), a key metabolite of interest is glycine. This disorder is characterized by elevated levels of glycine in the blood, urine, and cerebrospinal fluid due to a defect in the glycine cleavage system. Other metabolites that might be analyzed for diagnostic purposes include those in glycine metabolism pathways. However, glycine is the primary marker.
- Nutraceuticals
- Non-ketotic hyperglycinemia (NKH) is a rare genetic disorder characterized by an accumulation of glycine in the body's tissues and fluids. This elevation in glycine levels results from a defect in the glycine cleavage system. Nutraceuticals are not standard treatments for NKH, which is generally managed with medications like sodium benzoate to decrease glycine levels and potentially with dietary modifications to limit glycine intake. Current research does not support a significant role for nutraceuticals in the management of NKH. For specific treatment options, a healthcare provider specializing in metabolic disorders should be consulted.
- Peptides
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Non-ketotic hyperglycinemia (NKH), also known as glycine encephalopathy, is a rare genetic disorder caused by a defect in the glycine cleavage system, which leads to elevated levels of glycine in the body, particularly in the central nervous system. This condition primarily affects infants and can result in severe neurological symptoms, including developmental delays, seizures, and muscle hypotonia.
Peptides: In the context of NKH, elevated glycine, which is an amino acid and the simplest peptide, plays a key role. The disorder disrupts the normal breakdown of glycine, leading to its accumulation.
Nan: "Nan" is unclear in this context; if referring to a specific aspect of NKH, please provide more details.