Isovaleric Acidemia
Disease Details
Family Health Simplified
- Description
- Isovaleric acidemia is a rare genetic disorder characterized by the body's inability to properly break down the amino acid leucine, leading to a buildup of isovaleric acid.
- Type
- Isovaleric acidemia is a metabolic disorder and the type of genetic transmission is autosomal recessive.
- Signs And Symptoms
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Isovaleric acidemia (IVA) is an inherited metabolic disorder characterized by the body's inability to properly break down the amino acid leucine, leading to a buildup of isovaleric acid. The signs and symptoms of isovaleric acidemia can vary but often include:
- Vomiting
- Lethargy (lack of energy)
- Poor feeding in infants
- Seizures
- Coma in severe cases
- Sweaty feet odor, due to the accumulation of isovaleric acid
- Developmental delay and intellectual disability
It's important for individuals suspected of having IVA to receive prompt diagnosis and treatment to manage symptoms and prevent severe complications. - Prognosis
- A 2011 review of 176 cases found that diagnoses made early in life (within a few days of birth) were associated with more severe disease and a mortality of 33%. Children diagnosed later, and who had milder symptoms, showed a lower mortality rate of ~3%.
- Onset
- Isovaleric acidemia typically presents in infancy, often within the first few days or weeks after birth. There are also milder forms that can present later in childhood or even adulthood.
- Prevalence
- Isovaleric acidemia is a rare inherited metabolic disorder. The prevalence is estimated to be approximately 1 in 250,000 live births.
- Epidemiology
- Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States.
- Intractability
- Isovaleric acidemia is not inherently intractable but can be challenging to manage. It is a rare metabolic disorder that requires lifelong dietary management and careful monitoring to prevent metabolic crises. With early diagnosis and proper treatment, which often includes a low-protein diet and specific supplements, individuals with isovaleric acidemia can lead relatively normal lives. However, the complexity of the disorder can make management difficult in some cases.
- Disease Severity
- Isovaleric acidemia is a severe metabolic disorder that can lead to serious health complications if not managed properly. The severity can vary; some individuals may experience life-threatening symptoms in infancy, while others might present with milder symptoms later in life. Prompt diagnosis and treatment are crucial for managing the condition and improving the prognosis.
- Healthcare Professionals
- Disease Ontology ID - DOID:14753
- Pathophysiology
- The enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase (EC 1.3.99.10), plays an essential role in breaking down proteins from the diet. Specifically, the enzyme is responsible for the third step in processing leucine, an essential amino acid. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, isovaleric acid and related compounds build up to toxic levels, damaging the brain and nervous system.
- Carrier Status
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For isovaleric acidemia:
Carrier Status:
Isovaleric acidemia is an autosomal recessive disorder. Carrier status means an individual has one copy of the mutated gene but does not typically exhibit symptoms of the disease. Carriers can pass the gene to their offspring.
Nan:
If "nan" refers to a scientific term or abbreviation, please provide a clearer context or specification so that the appropriate information can be given. If "nan" was a typo or error, please clarify or restate your question. - Mechanism
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Isovaleric acidemia (IVA) is an autosomal recessive metabolic disorder caused by a deficiency in the enzyme isovaleryl-CoA dehydrogenase (IVD). This enzyme is crucial in the catabolic pathway of leucine, an essential amino acid.
### Mechanism:
IVA results in the accumulation of isovaleric acid and its derivatives in the blood, urine, and tissues due to the enzymatic block in the degradation of leucine. This accumulation can lead to various clinical manifestations, which may include metabolic acidosis, a distinct odor of sweaty feet, vomiting, lethargy, and, in severe cases, seizures or coma.
### Molecular Mechanisms:
1. **Genetic Mutation**: IVA is caused by mutations in the IVD gene, located on chromosome 15q15.1. These mutations lead to either a complete or partial loss of enzyme activity.
2. **Enzyme Deficiency**: The IVD enzyme normally catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA in the mitochondrial matrix. When IVD is deficient or non-functional, this conversion is impeded, causing an accumulation of isovaleryl-CoA.
3. **Metabolite Accumulation**: The buildup of isovaleryl-CoA is hydrolyzed to free isovaleric acid, which can interfere with several metabolic processes and cause toxicity to cells and tissues.
4. **Secondary Metabolic Effects**: The excess isovaleric acid can also impair mitochondrial function, disrupt the urea cycle, and affect neurotransmitter levels, contributing to the clinical manifestations of the disorder.
Early diagnosis and treatment, such as dietary restrictions on leucine intake and supplementation with glycine and carnitine, are critical to managing IVA and preventing severe metabolic crises. - Treatment
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Treatment consists of dietary protein restriction, particularly leucine. During acute episodes, glycine is sometimes given, which conjugates with isovalerate forming isovalerylglycine, or carnitine which has a similar effect.
Elevated 3-hydroxyisovaleric acid is a clinical biomarker of biotin deficiency. Without biotin, leucine and isoleucine cannot be metabolized normally and results in elevated synthesis of isovaleric acid and consequently 3-hydroxyisovaleric acid, isovalerylglycine, and other isovaleric acid metabolites as well. Elevated serum 3-hydroxyisovaleric acid concentrations can be caused by supplementation with 3-hydroxyisovaleric acid, genetic conditions, or dietary deficiency of biotin. Some patients with isovaleric acidemia may benefit from supplemental biotin. Biotin deficiency on its own can have severe physiological and cognitive consequences that closely resemble symptoms of organic acidemias. - Compassionate Use Treatment
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Isovaleric acidemia (IVA) is a rare metabolic disorder that involves the body's inability to properly break down leucine, an amino acid. For patients with IVA, a variety of treatment options can be considered when conventional treatments are insufficient:
1. **Glycine and L-carnitine Supplementation**: These compounds help to detoxify isovaleric acid and can be viewed as essential parts of IVA management. Glycine conjugates with isovaleric acid to form a less toxic compound, while L-carnitine helps to excrete the accumulating toxic metabolites.
2. **Dietary Management**: A low-protein diet supplemented with medical foods that contain essential amino acids minus leucine may be considered an off-label yet crucial approach to managing IVA by reducing the leucine load on the body.
3. **Emergency Regimen**: In cases of metabolic crisis, immediate medical intervention using intravenous glucose and lipids can help manage acute episodes. Though specific to crisis management, it can be seen as a vital part of the overall treatment strategy.
4. **Experimental Therapies**: Gene therapy and other genetic treatments are areas of active research. These experimental approaches aim to correct the underlying genetic defect in the IVD gene responsible for IVA. Outcomes from clinical trials are still awaited to establish their efficacy and safety conclusively.
These treatments are undertaken with careful consideration and monitoring by healthcare professionals to manage the disease effectively while minimizing potential risks. - Lifestyle Recommendations
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For individuals with isovaleric acidemia, lifestyle recommendations primarily revolve around managing diet and preventing metabolic crises. Here are some key suggestions:
1. **Specialized Diet**: Follow a low-protein diet to limit the intake of leucine, an amino acid that is improperly metabolized in isovaleric acidemia. Work with a dietitian to ensure nutritional needs are met despite dietary restrictions.
2. **Medical Supplements**: Use prescribed medical formulas that provide the necessary nutrients without including leucine.
3. **Frequent Meals**: Eat small, frequent meals to avoid extended fasting periods, which can trigger metabolic imbalances.
4. **Monitor for Symptoms**: Be vigilant for signs of metabolic crisis, such as vomiting, lethargy, or a distinctive odor resembling sweaty feet. Seek immediate medical attention if these symptoms occur.
5. **Emergency Plan**: Have a written emergency plan and easily accessible emergency medications like glycine and carnitine, which help to detoxify accumulated isovaleric acid.
6. **Regular Check-ups**: Maintain regular follow-ups with healthcare providers to monitor the condition and adjust dietary plans as necessary.
7. **Avoid Extreme Physical Stressors**: Minimize exposure to physical stressors like illness, fasting, or intense physical activity that can precipitate metabolic crises.
8. **Education and Support**: Educate family, friends, and caregivers about the condition and the importance of dietary and medical management. Seek support from communities or groups specializing in metabolic disorders.
These lifestyle adjustments help manage isovaleric acidemia effectively and prevent complications associated with the condition. - Medication
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In the management of isovaleric acidemia, the primary focus is on dietary modifications and specific medications to reduce the levels of isovaleric acid. Key medications include:
1. **Glycine**: This amino acid helps to conjugate and detoxify isovaleric acid, promoting its excretion.
2. **L-carnitine**: This compound helps to facilitate the excretion of certain toxic metabolites that accumulate in isovaleric acidemia.
3. **Antibiotics**: These may be used intermittently to reduce intestinal bacteria that produce isovaleric acid as a byproduct of protein metabolism.
Regular monitoring by a healthcare professional and adherence to dietary and medication regimens are crucial for managing this condition effectively. - Repurposable Drugs
- There is limited information on repurposable drugs specifically for isovaleric acidemia. Management typically involves dietary restrictions and the use of glycine and L-carnitine supplements to help with the detoxification of isovaleryl-CoA. If you're looking into experimental treatments, it would be best to consult with a specialist in metabolic disorders.
- Metabolites
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Isovaleric acidemia is a metabolic disorder that affects the way the body processes leucine, an amino acid. Metabolites associated with isovaleric acidemia include:
1. **Isovaleryl-CoA**
2. **Isovaleric acid**
3. **3-Hydroxyisovaleric acid**
4. **Isovalerylglycine**
Elevated levels of these metabolites, particularly isovaleric acid and isovalerylglycine, are typically observed in the blood and urine of affected individuals. - Nutraceuticals
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Isovaleric acidemia is a rare metabolic disorder characterized by a deficiency of the enzyme isovaleryl-CoA dehydrogenase. This condition leads to the accumulation of isovaleric acid, which can cause severe metabolic disturbances.
Nutraceuticals for isovaleric acidemia include supplements and dietary modifications designed to manage the symptoms and biochemical imbalances associated with the disorder. Common strategies involve:
1. Glycine: Used to conjugate with isovaleric acid to form isovalerylglycine, which is more easily excreted from the body.
2. L-carnitine: Helps to facilitate the excretion of toxic metabolites by forming isovalerylcarnitine.
3. Low-protein diet: Reduces the intake of leucine, thereby minimizing the production of isovaleric acid.
Maintaining a strict dietary regimen, alongside these nutraceuticals, can help in managing the condition effectively. Close monitoring by healthcare providers is crucial to ensure optimal outcomes. - Peptides
- Isovaleric acidemia is not directly associated with peptides as primary concern. It is a genetic metabolic disorder characterized by a deficiency of the enzyme isovaleryl-CoA dehydrogenase, which is involved in the breakdown of the amino acid leucine. Elevated levels of isovaleric acid can lead to a distinctive odor of sweaty feet, and the condition can result in poor feeding, vomiting, seizures, and even coma in severe cases. Treatment often involves dietary management to restrict leucine intake and use of medications such as glycine and carnitine to aid in the excretion of isovaleryl-CoA.