Summary about Disease
Isovaleric acidemia (IVA), also known as isovaleryl-CoA dehydrogenase deficiency, is an inherited metabolic disorder caused by a deficiency in the enzyme isovaleryl-CoA dehydrogenase (IVD). This enzyme is essential for breaking down leucine, an amino acid found in protein. When IVD is deficient, isovaleric acid and other harmful substances accumulate in the blood and urine, potentially leading to serious health problems. IVA is classified as an organic acidemia.
Symptoms
Symptoms can vary widely, ranging from severe, life-threatening conditions in newborns to milder, intermittent episodes later in life. Some individuals may never exhibit symptoms.
Acute/Severe Form (typically in newborns): Poor feeding, vomiting, lethargy, seizures, distinctive "sweaty feet" odor, coma. Can be life-threatening if not treated promptly.
Chronic/Intermittent Form: Episodes of vomiting, lethargy, developmental delays, intellectual disability, ataxia (loss of coordination), metabolic crisis triggered by infection or increased protein intake. The "sweaty feet" odor may or may not be present.
Causes
IVA is caused by mutations in the IVD gene. This gene provides instructions for making the isovaleryl-CoA dehydrogenase enzyme. Mutations in the *IVD* gene reduce or eliminate the activity of the enzyme. Defective enzyme leads to the accumulation of isovaleric acid and other harmful metabolites, which damage the brain and other organs. IVA is inherited in an autosomal recessive manner, which means both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Treatment focuses on reducing isovaleric acid levels and preventing build-up of other toxic substances.
Dietary Management: A low-protein diet, particularly restricting leucine intake, is crucial. Specialized formulas and foods low in leucine are often prescribed.
L-Carnitine Supplementation: L-carnitine helps to remove isovaleric acid from the body by binding to it and allowing it to be excreted in the urine.
Glycine Supplementation: Glycine can also help to remove isovaleric acid.
Emergency Treatment: During acute episodes, intravenous fluids, glucose, and medications to manage seizures or coma may be necessary.
Is Communicable
No, IVA is not communicable. It is a genetic disorder that is inherited. It cannot be spread from person to person through contact or any other means.
Precautions
Precautions mainly focus on preventing metabolic crises:
Dietary Control: Strict adherence to the prescribed low-leucine diet is essential.
Avoidance of Fasting: Prolonged periods without food should be avoided.
Prompt Treatment of Illnesses: Even minor illnesses can trigger a metabolic crisis. Sick days require adjustments to diet and potentially increased monitoring.
Monitoring: Regular monitoring of isovaleric acid levels and overall health is important.
Genetic Counseling: Genetic counseling is recommended for families with a history of IVA to understand the risk of recurrence.
How long does an outbreak last?
The duration of an acute metabolic crisis (or "outbreak") in IVA can vary significantly, from a few days to several weeks. It depends on the severity of the episode, how quickly it is recognized and treated, and the individual's overall health. Chronic, intermittent forms may have more frequent, but shorter, outbreaks.
Timeline of Symptoms
Newborns (Acute Form): Symptoms typically appear within the first few days or weeks of life.
Infancy/Childhood (Intermittent Form): Symptoms may not be apparent until later in infancy or childhood, often triggered by an illness, infection, or dietary indiscretion.
Adulthood: Some individuals may have milder forms that are not diagnosed until adulthood, or they may remain asymptomatic. The onset and severity of symptoms vary greatly depending on the individual.
Important Considerations
Early Diagnosis and Treatment: Early diagnosis and treatment are crucial to prevent severe complications, such as intellectual disability and neurological damage.
Lifelong Management: IVA requires lifelong management, including dietary restrictions, supplementation, and close monitoring.
Specialized Care: Individuals with IVA should be managed by a metabolic specialist and a team of healthcare professionals experienced in treating metabolic disorders.
Emergency Protocol: Families should have an emergency protocol in place for managing metabolic crises, including a letter for emergency room personnel outlining the condition and necessary treatment.
Support Groups: Support groups can provide valuable information and emotional support for families affected by IVA.