About isovaleric acid coa dehydrogenase deficiency

What is isovaleric acid co Dehydrogenase deficiency?

Isovaleric Acidemia is a hereditary metabolic disorder. It is characterized by a deficiency of the enzyme isovaleryl CoA dehydrogenase. The disorder occurs in both an acute and a chronic intermittent form. In the acute form of Isovaleric Acidemia, vomiting, refusal to eat, and listlessness usually occur. With treatment and low protein diet, the disorder becomes chronically intermittent, and a nearly normal life is possible.

What are the symptoms for isovaleric acid co Dehydrogenase deficiency?

Isovaleric acidemia is a rare metabolic disorder that ranges in severity from asymptomatic to mild or life-threatening symptoms depending on the mutation and factors predisposing acute attacks. Two major clinical scenarios are often described, an acute form and a chronic intermittent form, but in reality the disease is best thought of as a continuous spectrum from asymptomatic to life threatening. A characteristic ‘sweaty feet’ odor is often present in patient sweat or cerumen due to a buildup of isovaleric acid. Patients may develop aversion early to protein-rich foods.

Acute, early symptoms present soon after birth with increasing lethargy, poor feeding and vomiting, progressing to coma. These findings are related to chemical imbalances in the baby including an increase in acid, ammonia, and specific toxic compounds derived from isovaleric acid. Prolonged metabolic stress can lead to low levels of certain types of white blood cells (neutropenia) and other cell types (pancytopenia). Patients may also present with lowered body temperature (hypothermia). After resolution of this first attack, patients typically show the chronic intermittent form of the disease unless severe neurologic damage has occurred due to the original presentation.

After the newborn period chronic intermittent symptoms are usual. Patients can have slowed growth rates (failure to thrive), developmental delay, Intellectual disability or symptoms affecting the nervous system such as Seizures and spasticity, most commonly related to early acute damage. Patients can also experience acute attacks similar to the newborn period, typically triggered by other illnesses such as infections. Patients can exhibit a chronic picture even if a newborn acute attack has not occurred. Recognition of acute neonatal symptoms has led to newborn screening for isovaleric acidemia in the United States and many other developed studies. If identified prior to the development of symptoms, outcomes are generally better, with normal growth and development. About half of babies identified through newborn screening have a very mild deficiency that remains asymptomatic and requires no therapy.

What are the causes for isovaleric acid co Dehydrogenase deficiency?

Isovaleric acidemia is a genetic disorder inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

In patients with isovaleric acidemia, there is a mutation in the IVD gene that inactivates the enzyme isovaleryl-Co-enzyme A (CoA) dehydrogenase. This enzyme is needed for the breakdown of the amino acid leucine into energy.

What are the treatments for isovaleric acid co Dehydrogenase deficiency?

While there is no cure for isovaleric acidemia, the outcome is usually good if severe neonatal symptoms are avoided or treated rapidly. Patients should be followed regularly by a geneticist or metabolic physician familiar with the management of organic acidemias. The frequency of follow-up is determined by the severity of the disease and the frequency of acute attacks. The patient should be monitored for growth, development, and dietary history. Additional testing should include blood acid levels, blood counts, and electrolytes. Additionally, physicians may monitor for complications and do examinations of the nervous system, liver, or other organs.

What are the risk factors for isovaleric acid co Dehydrogenase deficiency?

Isovaleric acidemia is a rare disorder that presents either soon after birth or during infancy. It may present up to adolescence. It affects an equal number of males and females. The prevalence of this condition is 1 per 526,000 in Western populations and the incidence is 1 per 250,000 in the US.

Is there a cure/medications for isovaleric acid co Dehydrogenase deficiency?

Supplementation with L-carnitine or glycine allows increased removal of acids from the blood by the kidney. Patients typically require a low protein diet to avoid overconsumption of the amino acid leucine. However, patients need enough protein in their diet to meet the body’s demands, which increase over time with growth. However, it may be impossible for patients with severe diseases to eat enough natural protein to meet bodily requirements. In this case, the use of medical foods that do not include leucine is necessary. A dietician should be available to also help families with creating a low-protein diet for the patient.

During acute attacks, protein should be reduced or withheld for 24 hours with a subsequent increase in low protein, high sugar foods to maintain calorie intake. If a patient cannot eat, hospitalization is required so that glucose can be provided by intravenous fluids. Other metabolic abnormalities such as high ammonia may need to be corrected depending on the individual patient’s clinical findings. A return to the patient’s standard diet can usually be achieved over the course of a few days.

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