Carnitine Palmitoyl Transferase Ii Deficiency Severe Infantile Form
Disease Details
Family Health Simplified
- Description
- Carnitine palmitoyl transferase II (CPT II) deficiency severe infantile form is a rare genetic disorder characterized by the inability to properly metabolize long-chain fatty acids, leading to life-threatening episodes of hypoketotic hypoglycemia, cardiomyopathy, liver dysfunction, and muscle weakness in infancy.
- Type
- Carnitine palmitoyltransferase II (CPT II) deficiency, severe infantile form, is a metabolic disorder. It is inherited in an autosomal recessive pattern.
- Signs And Symptoms
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Carnitine palmitoyltransferase II deficiency (CPT II deficiency) in its severe infantile form typically presents with the following signs and symptoms:
1. **Hypoketotic hypoglycemia**: Low blood sugar levels with low ketone bodies.
2. **Hepatomegaly**: Enlarged liver.
3. **Cardiomyopathy**: Heart muscle disease, potentially leading to heart failure.
4. **Muscle Weakness**: Generalized weakness and potential muscle breakdown (rhabdomyolysis).
5. **Failure to thrive**: Poor weight gain and growth.
6. **Recurrent infections**: Possibly due to weakened immune function.
7. **Developmental delay**: Delays in reaching milestones.
Symptoms often begin in early infancy and can be exacerbated by fasting or illness. This form of CPT II deficiency is more severe compared to other forms and requires prompt medical attention. - Prognosis
- The prognosis for the severe infantile form of carnitine palmitoyltransferase II deficiency is generally poor. This form of the disorder typically presents within the first 6 to 24 months of life and is associated with severe symptoms including recurrent episodes of hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, and muscle weakness. Despite management strategies, many affected infants may not survive past early childhood due to these complications.
- Onset
- For the severe infantile form of Carnitine Palmitoyl Transferase II (CPT II) deficiency, the onset typically occurs within the first year of life, often between 6 months and 2 years of age. Symptoms can include hypoketotic hypoglycemia, hepatomegaly, cardiomyopathy, and muscle weakness.
- Prevalence
- The prevalence of the severe infantile form of Carnitine Palmitoyl Transferase II (CPT II) deficiency is not well-defined, but it is considered to be a rare genetic disorder.
- Epidemiology
- Carnitine palmitoyltransferase II deficiency, severe infantile form, is a rare genetic disorder, but specific epidemiological data such as incidence and prevalence rates are not well-documented due to its rarity. It affects infants and typically manifests between six and 24 months of age. The disorder is inherited in an autosomal recessive pattern.
- Intractability
- Carnitine palmitoyltransferase II deficiency, particularly the severe infantile form, is generally considered intractable. This form of the disease often presents with life-threatening symptoms early in life, such as hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, and muscle weakness. Despite treatment efforts, management is challenging and outcomes can be poor, making it a difficult condition to control effectively.
- Disease Severity
- Carnitine palmitoyltransferase II (CPT II) deficiency, in its severe infantile form, presents with a high degree of severity. This form typically manifests in early infancy with symptoms such as hypoketotic hypoglycemia, liver malfunction, cardiomyopathy, and muscle weakness. It is often life-threatening without prompt and appropriate medical treatment.
- Pathophysiology
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Carnitine palmitoyltransferase II (CPT II) deficiency, severe infantile form, is a metabolic disorder affecting the oxidation of long-chain fatty acids in mitochondria. The pathophysiology involves a deficiency or malfunction of the CPT II enzyme, which is crucial for transporting long-chain fatty acids from the cytoplasm into the mitochondria for beta-oxidation. This leads to an accumulation of long-chain fatty acids and their metabolites in cells, particularly impacting energy-demanding tissues like the liver, heart, and muscles.
Due to this defect, affected infants may present with hypoketotic hypoglycemia, cardiomyopathy, muscle weakness, hepatomegaly, and metabolic encephalopathy. Energy deficiencies in these tissues result in the clinical manifestations of the disorder, and episodes of metabolic crisis can be triggered by fasting, illness, or stress. - Carrier Status
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In the context of carnitine palmitoyltransferase II deficiency (CPT II deficiency), the severe infantile form is inherited in an autosomal recessive manner. This means that if an individual carries one mutated copy of the CPT2 gene (from one parent) and one normal copy (from the other parent), they are considered a carrier but typically do not show symptoms of the disorder.
Carriers of a single mutated CPT2 gene are generally asymptomatic. However, when two carriers have a child, there is a 25% chance with each pregnancy that the child will inherit two mutated copies of the gene (one from each parent) and thus develop the severe infantile form of CPT II deficiency. - Mechanism
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Carnitine palmitoyltransferase II deficiency (CPT II deficiency) is a metabolic disorder affecting fatty acid oxidation, particularly in the mitochondria.
**Mechanism:**
CPT II deficiency interrupts the carnitine shuttle, which is crucial for transporting long-chain fatty acids into the mitochondria for β-oxidation. Specifically, the CPT II enzyme, found on the inner mitochondrial membrane, converts acyl-carnitine back into acyl-CoA and free carnitine. In its absence or reduced activity, long-chain fatty acids cannot be efficiently utilized for energy production.
**Molecular Mechanisms:**
The severe infantile form of CPT II deficiency is typically caused by mutations in the CPT2 gene, leading to a significantly reduced or absent function of the CPT II enzyme. These mutations can alter enzyme structure, stability, or activity. As a result, accumulating long-chain acyl-carnitines can have cytotoxic effects, and the energy metabolism is impaired, especially in tissues with high-energy demands like the liver, muscles, and heart.
These disruptions manifest as hypoketotic hypoglycemia, hepatomegaly, cardiomyopathy, and muscle weakness, often appearing in infancy. - Treatment
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For the severe infantile form of carnitine palmitoyltransferase II deficiency, treatment primarily includes:
1. **Dietary Modifications**:
- A high-carbohydrate, low-fat diet with medium-chain triglycerides (MCTs) can be beneficial.
- Frequent meals to avoid long periods of fasting, which can trigger metabolic crises.
2. **Medications**:
- Carnitine supplements may be administered to increase the levels of free carnitine available in the body.
- Triheptanoin (an odd-chain fatty acid triglyceride) might also be considered.
3. **Avoidance of Triggers**:
- Avoid excessive physical exertion, fasting, and exposure to cold, as these can precipitate symptoms.
4. **Symptomatic Treatment**:
- Management of acute episodes includes intravenous glucose and fluids to provide energy and prevent further muscle breakdown.
Regular follow-up with a metabolic specialist is crucial to monitor and adjust treatment as necessary. - Compassionate Use Treatment
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Carnitine palmitoyltransferase II deficiency, severe infantile form, is a rare metabolic disorder affecting the oxidation of long-chain fatty acids in mitochondria. For this condition, the following options are considered under compassionate use, off-label, or experimental treatments:
1. **High-Carbohydrate, Low-Fat Diet:** Reducing the intake of long-chain fatty acids while increasing carbohydrates can help manage symptoms.
2. **Medium-Chain Triglycerides (MCT):** Supplementing with MCTs can provide an alternative energy source that bypasses the defective enzyme.
3. **Triheptanoin (UX007):** Although primarily used for long-chain fatty acid oxidation disorders, Triheptanoin is being explored for CPT II deficiency under experimental access through clinical trials or compassionate use programs.
4. **Riboflavin:** Some cases have shown improvement with riboflavin supplementation, suggesting a potential off-label treatment.
5. **Gene Therapy:** Experimental approaches to directly correct the genetic mutation involved are under preliminary investigation.
Consultation with a metabolic specialist and genetic counselor is essential for tailored treatment approaches. - Lifestyle Recommendations
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For severe infantile form of Carnitine Palmitoyl Transferase II (CPT II) deficiency, lifestyle recommendations include:
1. **Dietary Management**:
- **High-Carbohydrate, Low-Fat Diet**: This helps to reduce reliance on fatty acid oxidation for energy.
- **Frequent Meals**: Prevents fasting and maintains blood glucose levels. Infants may require night feedings.
- **Medium-Chain Triglycerides (MCTs)**: These fats can be more easily metabolized and are often included in the diet.
2. **Exercise Management**:
- **Moderate Intensity**: Engage in physical activities that avoid extreme exertion, which can trigger symptoms.
3. **Avoidance of Fasting**:
- **Regular Feeding Schedule**: Ensures continuous energy supply and prevents metabolic stress.
4. **Supplementation**:
- **L-Carnitine**: Can be used under medical supervision to support muscle function and energy production.
5. **Medical Monitoring**:
- **Regular Check-ups**: With a focus on metabolic and nutritional status.
6. **Infection Control**:
- **Preventing Infections**: Illness can exacerbate symptoms. Vaccinations and good hygiene are crucial.
These recommendations should be customized based on individual needs and under a healthcare provider's supervision. - Medication
- There is no specific medication for the severe infantile form of Carnitine Palmitoyl Transferase II (CPT II) deficiency. Management primarily focuses on dietary modifications and supportive care. A high-carbohydrate, low-fat diet supplemented with medium-chain triglycerides (MCTs) can be beneficial. Immediate treatment during metabolic crises may involve intravenous glucose and other supportive measures in a medical setting. Avoidance of fasting, strenuous exercise, and other stressors that can precipitate symptoms is also crucial. Consultation with a metabolic specialist is recommended for individualized management plans.
- Repurposable Drugs
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For severe infantile form of Carnitine Palmitoyltransferase II (CPT II) deficiency, there is limited specific information available about repurposable drugs. The focus of management typically includes dietary modifications such as a high-carbohydrate, low-fat diet with medium-chain triglyceride (MCT) supplementation to bypass the metabolic block.
Some potential therapeutic agents or measures that might be considered (though not specific "repurposable drugs") include:
1. **L-Carnitine Supplementation**: To help transport fatty acids into the mitochondria.
2. **Triglyceride Oils**: Medium-chain triglycerides (MCT) can provide an alternative energy source.
3. **Riboflavin (Vitamin B2)**: There have been reports suggesting benefits in some metabolic conditions.
However, it is crucial to consult with a healthcare provider or a metabolic specialist for precise therapeutic strategies tailored to the specific condition and patient needs. Clinical trials and emerging research should be monitored for potential new treatments. - Metabolites
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In the severe infantile form of Carnitine Palmitoyltransferase II (CPT II) deficiency, the following metabolic abnormalities are typically observed:
- Elevated levels of long-chain acylcarnitines in the blood, particularly C16 and C18:1 species.
- Low levels of free carnitine.
- Presence of dicarboxylic acids and medium-chain acylcarnitines in urine.
These metabolic markers are indicative of impaired fatty acid oxidation due to the deficiency in CPT II enzyme activity. - Nutraceuticals
- Carnitine palmitoyltransferase II (CPT II) deficiency, severe infantile form, is a rare genetic disorder that affects fatty acid oxidation. Currently, there is limited evidence on the efficacy of nutraceuticals in treating this condition. Management typically focuses on dietary modifications, such as a high-carbohydrate, low-fat diet, and avoiding long periods of fasting. Any use of nutraceuticals should be discussed with a healthcare professional.
- Peptides
- Carnitine palmitoyltransferase II deficiency (CPT II deficiency) is a metabolic disorder affecting fatty acid oxidation. In the severe infantile form, peptides and nan (presumably meaning nanomolar concentrations of specific substances) are not typically the focus of treatment or diagnosis. Instead, this condition is diagnosed through genetic testing and measurement of enzyme activity. Treatment generally involves preventive measures like a high-carbohydrate, low-fat diet, supplementation with medium-chain triglycerides (MCTs), and avoiding fasting to prevent metabolic crises. Early diagnosis and management are crucial to mitigate symptoms such as hypoglycemia, liver dysfunction, and muscle weakness.