Multiple Acyl-coa Dehydrogenase Deficiency
Disease Details
Family Health Simplified
- Description
- Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a metabolic disorder characterized by the body's inability to break down certain fats and proteins for energy, leading to a range of symptoms including muscle weakness, hypoglycemia, and metabolic crises.
- Type
- Multiple acyl-CoA dehydrogenase deficiency (MADD) is a metabolic disorder. It is inherited in an autosomal recessive manner.
- Signs And Symptoms
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Signs and symptoms of Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) can vary widely among affected individuals but commonly include:
1. **Muscle Weakness**: This can be episodic or persistent and may affect both skeletal and cardiac muscles.
2. **Hypotonia**: Low muscle tone, particularly in infants.
3. **Hypoglycemia**: Low blood sugar levels, which might cause symptoms such as irritability, sweating, and seizures.
4. **Failure to Thrive**: Poor growth or weight gain in infants.
5. **Metabolic Acidosis**: High levels of acid in the blood, possibly leading to rapid breathing, fatigue, and nausea.
6. **Fatty Liver**: Accumulation of fat in liver cells.
7. **Developmental Delay**: Delayed physical and cognitive development.
8. **Vomiting and Lethargy**: General malaise and decreased energy.
9. **Liver Dysfunction**: May present with elevated liver enzymes.
10. **Cardiomyopathy**: Disease of the heart muscle, leading to possible heart failure.
11. **Respiratory Distress**: Breathing difficulties.
These symptoms can range from mild to severe and may present at various points in life, from neonates to adults. Early diagnosis and management are crucial to improving outcomes. - Prognosis
- Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, has a highly variable prognosis depending on the severity and onset of the condition. In neonatal-onset cases with congenital anomalies, the prognosis is generally poor with high mortality. In milder, later-onset forms, individuals may respond well to treatment and have a more favorable prognosis, but they may still experience episodes of metabolic decompensation that can lead to significant morbidity. Early diagnosis and appropriate management, including dietary modifications and supplementation with riboflavin and coenzyme Q10, can improve outcomes.
- Onset
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The onset of multiple acyl-CoA dehydrogenase deficiency (MADD) can vary widely. There are three primary forms of this condition based on the age of onset:
1. **Neonatal onset with congenital anomalies**: Symptoms appear in the newborn period and can be severe, often including congenital anomalies and metabolic crises.
2. **Neonatal onset without congenital anomalies**: Symptoms also appear shortly after birth but without associated congenital anomalies. These infants can experience severe metabolic issues.
3. **Later-onset form**: Symptoms can appear from infancy to adulthood. This form usually presents with muscle weakness, episodes of metabolic decompensation, and other less severe symptoms compared to the neonatal forms.
Early detection and management are crucial for better outcomes. The specific age of onset and severity can depend on the individual and the particular genetic mutations involved. - Prevalence
- Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a rare metabolic disorder. The prevalence of MADD is not well defined but is estimated to be less than 1 in 100,000 live births.
- Epidemiology
- Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a rare inherited metabolic disorder caused by mutations in the genes ETFA, ETFB, or ETFDH. The exact worldwide prevalence of MADD is not well established, but it is considered to be very rare. It typically manifests in early infancy but can present at any age. Due to its rarity, epidemiological data is limited and may vary regionally.
- Intractability
- Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a genetic disorder that affects the body's ability to break down certain fats and proteins for energy. The intractability of the disease varies depending on the severity and type of the disorder. In milder forms, symptoms can be managed with dietary modifications and supplements like riboflavin. However, more severe cases may be more challenging to treat and can result in significant health issues. Early diagnosis and intervention are crucial for better management of the disease.
- Disease Severity
- Multiple acyl-CoA dehydrogenase deficiency (MADD) can range in severity from mild to severe. This metabolic disorder affects the body's ability to break down certain fats and proteins to produce energy. In its mild form, symptoms may include muscle weakness or exercise intolerance. In severe cases, it can present in infancy or early childhood with life-threatening metabolic crises, liver disease, developmental delay, and other serious complications.
- Healthcare Professionals
- Disease Ontology ID - DOID:0060358
- Pathophysiology
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Multiple acyl-CoA dehydrogenase deficiency (MADD) is a genetic disorder affecting fatty acid, amino acid, and choline metabolism. It is caused by mutations in the ETFA, ETFB, or ETFDH genes that encode proteins involved in the electron transport chain within mitochondria. These mutations impair the normal function of acyl-CoA dehydrogenases, enzymes critical for the dehydrogenation steps in the breakdown of fatty acids. As a result, the body cannot effectively convert fats into energy, leading to an accumulation of fatty acids and secondary metabolites, which can cause cellular and tissue damage.
Nan (not applicable): Additional information under the heading "nan" seems to be either a placeholder or irrelevant in the context of this inquiry. Please provide specific terms or queries to facilitate further discussion. - Carrier Status
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For Multiple Acyl-CoA Dehydrogenase Deficiency (MADD):
Carrier Status: MADD is an autosomal recessive disorder. This means that individuals who have one copy of the mutated gene and one normal gene are carriers of the condition but typically do not show symptoms. Carriers can pass the mutated gene to their offspring.
Nan: The term "nan" does not apply to MADD, so it is unclear what specific information you are referring to. Please provide additional context if you have other specific questions about the disease. - Mechanism
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Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a metabolic disorder that impairs the body's ability to break down fats and proteins for energy.
Mechanism:
MADD is primarily caused by mutations in genes that code for either the electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO), vital components of the mitochondrial electron transport chain. These proteins are essential for transferring electrons from acyl-CoA dehydrogenases to the electron transport chain, facilitating fatty acid and amino acid oxidation.
Molecular mechanisms:
1. **ETF Mutations (ETFA or ETFB genes)**: Mutations in the ETFA or ETFB genes lead to dysfunctional ETF proteins, disrupting electron transfer from multiple acyl-CoA dehydrogenases to the electron transport chain. This impedes the oxidation of fatty acids and amino acids, causing an accumulation of toxic intermediates and a deficit in ATP production.
2. **ETF-QO Mutations (ETFDH gene)**: Mutations in the ETFDH gene result in defective ETF-QO protein, further inhibiting electron transfer processes. Similar to ETF defects, this results in the accumulation of metabolic intermediates and insufficient ATP production.
3. **Accumulation of Metabolites**: Impaired activity of ETF or ETF-QO leads to the buildup of acyl-carnitines, organic acids, and other metabolites in tissues and biological fluids, contributing to metabolic crises and organ dysfunction.
Overall, the dysfunction in these proteins leads to a broad-based deficiency in the oxidation of various substrates, causing the clinical manifestations of MADD. - Treatment
- It is important for patients with MADD to strictly avoid fasting to prevent hypoglycemia and crises of metabolic acidosis; for this reason, infants and small children should eat frequent meals. Patients with MADD can experience life-threatening metabolic crises precipitated by common childhood illnesses or other stresses on the body, so avoidance of such stresses is critical. Patients may be advised to follow a diet low in fat and protein and high in carbohydrates, particularly in severe cases. Depending on the subtype, riboflavin (100-400 mg/day), coenzyme Q10 (CoQ10), L-carnitine, or glycine supplements may be used to help restore energy production. Some small, uncontrolled studies have reported that racemic salts of beta-hydroxybutyrate (one of the ketone bodies) were helpful in patients with moderately severe disease; further research is needed.
- Compassionate Use Treatment
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Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a genetic metabolic disorder affecting fatty acid, amino acid, and choline metabolism. Compassionate use and experimental treatments for MADD mainly involve:
1. **Riboflavin (Vitamin B2)**: While not experimental, high doses of riboflavin can be effective, particularly in the riboflavin-responsive form of MADD.
2. **Dichloroacetate (DCA)**: This is an investigational treatment that can help reduce the buildup of toxic intermediates by activating an enzyme called pyruvate dehydrogenase.
3. **Ketogenic Diet**: Though primarily used for other metabolic disorders, ketogenic diets can sometimes help manage symptoms by providing an alternative energy source that bypasses defective fatty acid oxidation pathways.
4. **L-carnitine Supplementation**: This is used to help reduce the buildup of acyl-CoA compounds and support energy production, though its effectiveness can vary.
5. **Coenzyme Q10 and Other Antioxidants**: These can support mitochondrial function and reduce oxidative stress, which might help alleviate some symptoms.
Compassionate use of these treatments is generally considered when standard therapies do not provide adequate control of the disease symptoms. Always consult with a healthcare professional for the most appropriate and current treatment options. - Lifestyle Recommendations
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Multiple acyl-CoA dehydrogenase deficiency (MADD) is a metabolic disorder affecting the body's ability to break down fats, proteins, and carbohydrates for energy. Lifestyle recommendations for managing this condition include:
1. **Dietary Management**:
- **High-Carbohydrate, Low-Fat Diet**: Emphasize complex carbohydrates while limiting fat intake to reduce the reliance on fatty acid oxidation for energy.
- **Frequent Meals**: Eating smaller, more frequent meals can help maintain blood sugar levels and provide a steady energy supply.
- **Protein Management**: Moderate protein intake, avoiding excessive protein that the body may struggle to metabolize.
- **Avoiding Prolonged Fasting**: Regular meals to prevent the body from entering a catabolic state where it might start breaking down fats and proteins for energy.
2. **Supplementation**:
- **Riboflavin (Vitamin B2)**: Some individuals may benefit from riboflavin supplements, as it plays a role in the function of the mitochondrial enzyme complexes affected by MADD.
- **Carnitine**: May be prescribed to help transport fatty acids into mitochondria for energy production and to prevent toxic buildup of fatty acids.
3. **Exercise**:
- **Moderate Physical Activity**: Engage in light to moderate exercise, but avoid high-intensity workouts that can increase energy demands and risk of metabolic crisis.
- **Energy Monitoring**: Be aware of signs of energy deficiency during physical activities and adjust efforts accordingly.
4. **Avoiding Stressors**:
- **Stress Management**: Reduce physical and emotional stress that can increase metabolic demands.
- **Illness Prevention**: Prevent infections and illnesses, as they can increase energy requirements and risk a metabolic crisis.
5. **Regular Medical Follow-up**:
- Regular check-ups with healthcare providers specializing in metabolic disorders for monitoring and adjustments in management strategies.
These lifestyle changes aim to minimize metabolic stress and manage symptoms effectively. - Medication
- For multiple acyl-CoA dehydrogenase deficiency (MADD), medication often includes riboflavin (vitamin B2) as a first-line treatment to improve enzyme activity. Coenzyme Q10 and L-carnitine supplements may also be prescribed to support energy production and fatty acid metabolism. A specialized diet low in fatty acids and high in carbohydrates might be recommended to manage symptoms. Always consult with a healthcare provider for personalized treatment plans.
- Repurposable Drugs
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Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II, is a genetic metabolic disorder affecting fatty acid, amino acid, and choline metabolism. For MADD, some repurposable drugs include:
1. **Riboflavin (Vitamin B2)**: Some patients respond to high doses of riboflavin, which acts as a cofactor for the enzyme complex affected in MADD.
2. **Coenzyme Q10 (Ubiquinone)**: Used to support mitochondrial function, which can be compromised in MADD.
3. **Carnitine**: May be supplemented to help with the transport of fatty acids into mitochondria for energy production.
These treatments may help manage symptoms and improve metabolic stability in some patients. Always consult with a healthcare provider for an individualized approach. - Metabolites
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Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a metabolic disorder that affects the body's ability to break down certain fats and proteins. This leads to the accumulation of various metabolites, including:
1. **Elevated Organic Acids**:
- Glutaric acid
- Ethylmalonic acid
- 3-Hydroxyisovaleric acid
- Suberylglycine
2. **Acylcarnitines**:
- Increased levels of short, medium, and long-chain acylcarnitines detected on acylcarnitine profile
These metabolite accumulations are indicative of MADD and are often detected through urine organic acid analysis and plasma acylcarnitine profiling. Elevated metabolites can provide crucial diagnostic information for this condition. - Nutraceuticals
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Multiple acyl-CoA dehydrogenase deficiency (MADD) is a genetic disorder that affects the body's ability to break down fats and proteins for energy. The use of nutraceuticals in MADD focuses on dietary management to compensate for the metabolic deficiencies. Common approaches include:
1. **Riboflavin (Vitamin B2):** High doses can be beneficial as riboflavin is a cofactor for acyl-CoA dehydrogenase enzymes.
2. **Coenzyme Q10 and Carnitine:** These supplements may help in improving energy production at the cellular level.
3. **Medium-Chain Triglycerides (MCTs):** They can be more easily utilized for energy compared to long-chain fatty acids.
Nanotechnology-based approaches are still in the experimental stages and are not widely used in clinical settings for MADD. Research is ongoing to explore the potential of nanomedicine in improving the delivery and efficacy of treatments. - Peptides
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Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a metabolic disorder that affects the body's ability to break down certain fats and proteins. It is caused by mutations in the genes ETFA, ETFB, or ETFDH. These genes encode components of the electron transfer flavoprotein and its dehydrogenase, which are essential for the mitochondrial fatty acid β-oxidation process.
In MADD, the defective enzymes hinder the normal breakdown of fatty acids and amino acids, leading to an accumulation of these substances and their byproducts, which can be toxic. Symptoms can vary widely but may include muscle weakness, hypoglycemia, metabolic acidosis, and, in severe cases, organ dysfunction.
Diagnosis typically involves biochemical tests showing elevated levels of certain metabolites in blood and urine, genetic testing, and, in some cases, enzyme activity assays. Treatment often includes dietary management to avoid fasting and the use of special nutritional supplements, such as riboflavin (vitamin B2) and carnitine, to support metabolic processes.