Isovaleric acidemia (IVA) is a rare condition that children can inherit from both their biological parents. It can cause serious problems with how the body breaks down proteins.

IVA causes an inability to break down leucine, an amino acid that is part of proteins in foods such as meat and fish. Humans usually have an enzyme that breaks leucine down into isovaleric acid, a substance that provides energy. People who cannot break this down end up with too much isovaleric acid in their system.

This can lead to dangerous episodes of worsening symptoms called metabolic crises. However, people can manage the condition and reduce their number of crises using specialist diets and medication.

Read on to learn more about the symptoms and causes of IVA. This article also looks at diagnosis, treatment options, and more.

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Symptoms of IVA may develop throughout childhood. In severe cases, symptoms may appear within a few days after birth.

However, the IVA symptoms can differ between people. Symptoms may also come and go.

Within a few weeks of birth, symptoms might include:

Symptoms of IVA also include:

Metabolic crisis symptoms

Infants with the acute form of IVA may have more severe symptoms from birth. A metabolic crisis can present with the following symptoms:

This is a medical emergency. Without treatment, a metabolic crisis can lead to convulsions, where the muscles contract uncontrollably, and coma. It can also be fatal.

A chronic intermittent type of IVA might also present. This leads to symptoms that occur and then resolve.

A person inherits IVA due to changes in their genes, the building blocks of DNA.

IVA occurs when there is a mutation in the gene coding for an enzyme called isovaleryl-CoA dehydrogenase (IVD), resulting in a deficiency of typical IVD.

Several factors may trigger IVA episodes, including infections and a large intake of food that is high in protein.

People inherit IVA in an autosomal recessive pattern. This means that both biological parents must pass on altered IVD genes for the condition to develop. Parents will carry a single copy of the gene without showing symptoms.

When two people with these genes have a baby, the infant will have a 25% chance of developing IVA. There is a 50% chance that the child will inherit one copy of the gene and become a carrier of IVA.

Doctors can identify IVA through a blood test called tandem mass spectrometry. They may order the test as part of routine screening in newborns.

If a person has symptoms of IVA, their doctor may order various laboratory tests to check for the following:

  • ketoacidosis, which refers to high levels of acid and ketones
  • hyperglycinemia and hyperglycinuria, where a person has high levels of glycerine in the blood and urine
  • neutropenia, which is when there are low levels of certain white blood cells
  • thrombocytopenia, where a person has low levels of platelets
  • pancytopenia, where a person has low levels of all blood cell types

A DNA test can help confirm the diagnosis.

If a person has a child with IVA, it may be possible to diagnose the condition prenatally in any future pregnancies.

It is best to contact a doctor if there are concerns about IVA. They can advise on any tests they recommend to help reach an accurate diagnosis.

Screening can help detect IVA before a person experiences noticeable symptoms. Doctors screen newborns using a tiny amount of blood from the infant’s heel. This is called blood spot screening.

The screening checks for levels of a substance called acylcarnitines that develop when they break down food. High acylcarnitine levels might indicate IVA.

A doctor may also recommend prenatal tests to screen for IVA in a fetus if the parents have another child with IVA.

Treatment for IVA involves:

  • managing the diet
  • taking medications that promote the breakdown of excess isovaleric acid
  • managing metabolic crises with emergency treatment


People with IVA need to avoid eating high protein foods, including:

This also includes breast milk, which provides too much leucine. An infant with IVA will not be able to break this down.

A registered dietitian can recommend alternatives to breast milk, including a protein-free milk formula. This will contain other amino acids and all the necessary vitamins and minerals to support a growing infant.

Dietary changes are lifelong for people with IVA. A dietitian can advise on changing the diet as an infant grows.

Learn more about foods that are high in protein.


Prescription medications that can reduce the amount of leftover valeric acid include L-carnitine and glycine. Some people may need to take both.

Emergency diet

The risk of a metabolic crisis becomes higher if a child catches a cold or other tract infection. During this time, a child may need to follow an emergency diet consisting of specialized, high sugar drinks.

A dietitian can also provide instructions on using an at-home feeding tube for periods of illness.

When to call the ER

It is important to contact the metabolic team at the nearest hospital if a child with IVA vomits up their emergency fluids or regularly has diarrhea during feeding.

People should let ER staff know that the child will be attending. The child’s doctor should have provided a leaflet describing the necessary treatment. As IVA is a rare condition, the medical team may not have treated it before.

Parents or caregivers should take a child with IVA to the ER if they show signs of the following:

IVA is extremely rare. It affects fewer than 5,000 people in the United States.

The National Library of Medicine estimates that the condition affects 1 in 250,000 people in the U.S. According to the Health Resources and Services Administration, fewer than 20 babies are born with IVA in the U.S. every year.

Children with IVA can live a long, healthy life and develop within typical ranges. However, they will need to continue treatment for the rest of their lives.

According to a 2012 study of 176 people with IVA, the diagnosis of IVA symptoms near birth usually has links to an increased risk of developmental delays and mortality.

A person’s doctor can provide more information about their outlook based on their individual circumstances.

Isovaleric acidemia (IVA) is a rare inherited condition that affects leucine breakdown.

People with IVA cannot process foods that are high in protein. Symptoms can show at any time but are particularly severe if they show in infants. A blood spot screening can help a doctor identify IVA.

After an IVA diagnosis, people will need to avoid high protein food and take lifelong medications to clear waste acids from the body. However, those with IVA can have a typical life expectancy with effective treatment.