Summary about Disease
Isovaleric acidemia (IVA), also known as isovaleric aciduria, is a rare inherited metabolic disorder in which the body is unable to properly break down the amino acid leucine. Leucine is found in protein-containing foods. This breakdown deficiency leads to a buildup of isovaleric acid in the blood, which is toxic and can cause severe health problems if not managed. IVA is classified as an organic acidemia.
Symptoms
Symptoms can vary depending on the severity of the condition. Some individuals may have a severe, acute form, while others have a milder, chronic form.
Acute Form (most common in newborns):
Poor feeding
Vomiting
Lethargy
Seizures
Coma
Distinctive "sweaty feet" odor due to the buildup of isovaleric acid.
Chronic/Intermittent Form:
Episodes (attacks) triggered by illness, high protein intake, or stress.
Symptoms during attacks can include vomiting, lethargy, and developmental delays.
Between attacks, individuals may be relatively symptom-free.
Causes
IVA is caused by mutations in the IVD gene. This gene provides instructions for making an enzyme called isovaleryl-CoA dehydrogenase. This enzyme is essential for the breakdown of leucine. When the *IVD* gene is mutated, the enzyme is deficient or absent, leading to the accumulation of isovaleric acid. IVA 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
The primary goal of treatment is to reduce the buildup of isovaleric acid. Medications used may include:
Glycine: Helps the body eliminate isovaleric acid by combining with it to form a less toxic compound that can be excreted in the urine.
L-Carnitine: Helps to remove isovaleric acid and other harmful compounds from the body.
Antibiotics: In some cases, antibiotics may be used to reduce the amount of isovaleric acid produced by bacteria in the gut.
Intravenous fluids and glucose: During acute episodes, IV fluids and glucose can help provide energy and prevent the breakdown of muscle tissue, which can release more leucine.
Is Communicable
No, isovaleric acidemia is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
Precautions primarily involve dietary management and preventing triggers:
Dietary Management: Following a strict low-protein diet, especially restricting leucine intake, is crucial. A dietitian specializing in metabolic disorders is essential for developing an appropriate meal plan.
Avoidance of Fasting: Prolonged periods without food should be avoided, as fasting can trigger the breakdown of muscle tissue and increase leucine levels.
Prompt Treatment of Illnesses: Any illness or infection should be treated promptly to prevent metabolic decompensation.
Emergency Protocol: Families should have an emergency protocol in place for managing acute episodes, including knowing when to seek medical attention and having access to emergency medications.
Monitoring: Regular monitoring of isovaleric acid levels and other relevant metabolites is necessary to adjust treatment as needed.
How long does an outbreak last?
The duration of an acute metabolic crisis (outbreak) varies. With prompt treatment, an acute episode may last from a few days to a week. Without treatment, acute episodes can be life-threatening. The chronic/intermittent form is characterized by recurring episodes throughout life.
How is it diagnosed?
Diagnosis typically involves:
Newborn Screening: Many states include IVA in their newborn screening programs. This involves analyzing a blood sample for elevated levels of isovalerylcarnitine.
Urine Organic Acid Analysis: Detects elevated levels of isovaleric acid and other abnormal organic acids in the urine.
Plasma Amino Acid Analysis: Measures the levels of amino acids in the blood, including leucine.
Genetic Testing: Confirms the diagnosis by identifying mutations in the IVD gene.
Enzyme Assay: Measures the activity of isovaleryl-CoA dehydrogenase in white blood cells or cultured skin cells (fibroblasts).
Timeline of Symptoms
Newborn Period (Acute Form): Symptoms may appear within the first few days or weeks of life.
Infancy/Childhood (Chronic/Intermittent Form): Symptoms may not appear until later in infancy or childhood, and episodes may be triggered by illness, high protein intake, or stress.
Throughout Life: Individuals with the chronic form may experience recurrent episodes throughout their lives.
Important Considerations
Early Diagnosis and Treatment: Early diagnosis through newborn screening and prompt treatment are critical to preventing severe complications and improving outcomes.
Lifelong Management: IVA requires lifelong dietary management and medical supervision.
Genetic Counseling: Genetic counseling is recommended for families with a history of IVA to assess the risk of recurrence in future pregnancies.
Support Groups: Support groups can provide valuable resources and support for families affected by IVA.
Metabolic Decompensation: Understanding the signs and symptoms of metabolic decompensation is essential for preventing life-threatening complications.