SCOT deficiency is a metabolic disease that is caused by reduced or missing levels of an enzyme called succinyl-CoA:3-ketoacid CoA transferase (SCOT). This enzyme is necessary for the body to use ketones. Ketones are substances produced in the liver when fats are broken down. Ketones are an important source of energy, especially when there is a shortage of carbohydrates (sugar). SCOT deficiency is characterized by episodes of ketoacidosis (build-up of ketones in the body). Symptoms of ketoacidosis may vary but can include trouble breathing, poor feeding, vomiting, and lethargy. In some cases, the symptoms can progress to include loss of consciousness and a coma. In between these episodes, individuals with SCOT deficiency do not have any symptoms.

SCOT deficiency is caused by mutations (changes) in the OXCT1gene. The disease is inherited in an autosomal recessive manner. SCOT deficiency can be diagnosed by ruling out other causes of ketoacidosis and measuring the level of SCOT enzyme. Genetic testing of the OXCT1 gene can be used to confirm the diagnosis. Immediate treatment of ketoacidotic crises is critical. Treatment options include IV fluids such as glucose and sodium bicarbonate. Frequent meals and eating a diet low in fats is important to reduce the frequency of ketoacidotic crises.

OXCT1 gene. This gene provides the body with instructions for how to create an enzyme called succinyl-CoA:3-ketoacid CoA transferase (SCOT). The SCOT enzyme helps the body break down ketones to be used for energy. When there are mutations in the OXCT1 gene, the body does not make enough of the SCOT enzyme. This causes the body to be unable to break down ketones. When ketones cannot be broken down, they begin to accumulate in the blood and the body does not have enough energy. This causes the symptoms of SCOT deficiency.

It is especially important for the body to be able to break down ketones when there is not other energy available to the body through glucose (sugars). Ketones are most frequently used for energy during times of fasting between meals, illness, or stress. These are the times when symptoms of SCOT deficiency are most likely to occur.

Normal Function

The OXCT1 gene provides instruction for making an enzyme called succinyl-CoA:3-ketoacid CoA transferase, often abbreviated as SCOT. The SCOT enzyme is made in the energy-producing centers of cells (mitochondria). The enzyme plays a role in the breakdown of ketones, which are molecules produced by the liver during the breakdown of fats. Ketones are an important source of energy during prolonged periods without food (fasting) or when energy demands are increased, such as during illness or when exercising. In the processing of ketones, the SCOT enzyme converts the molecule acetoacetate to acetoacetyl-CoA.

Health Conditions Related to Genetic Changes

Succinyl-CoA:3-ketoacid CoA transferase deficiency

At least 20 mutations in the OXCT1 gene have been found to cause SCOT deficiency, a condition characterized by episodes of extreme tiredness, appetite loss, and seizures, known as ketoacidotic attacks. Most OXCT1 gene mutations lead to changes in single protein building blocks (amino acids) in the SCOT enzyme and result in an enzyme with little or no function. A reduction in the amount of functional enzyme leads to an inability to break down ketones, often resulting in decreased energy production and an elevated level of ketones in the blood. If these signs become severe, a ketoacidotic attack can occur.

Other Names for This Gene

• 3-oxoacid CoA transferase 1
• 3-oxoacid-CoA transferase 1
• OXCT
• SCOT
• SCOT1_HUMAN
• somatic-type succinyl CoA:3-oxoacid CoA-transferase
• somatic-type succinyl-CoA:3-oxoacid-CoA-transferase
• succinyl CoA:3-oxoacid CoA transferase
• succinyl-CoA:3-ketoacid-CoA transferase
• succinyl-CoA:3-ketoacid-coenzyme A transferase 1, mitochondrial

Genomic Location

The OXCT1 gene is found on chromosome 5.

OXCT1gene must be changed in order to have symptoms of the disease. We inherit one copy of each gene from our mother and the other from our father.

People with a mutation in only one copy of the OXCT1 gene are known as carriers. Most carriers do not have any symptoms of the disease, although some may experience ketoacidotic crises during times of stress. When two carriers of SCOT deficiency have children together, for each child there is a:

• 25% chance that the child will have SCOT deficiency
• 50% chance that the child will be a carrier of SCOT deficiency like the parents
• 25% chance that the child will have two working copies of OXCT1, so the child will not have SCOT deficiency and will not be a carrier.

Symptoms of ketoacidosis may vary but can include rapid breathing (tachypnea), poor feeding, vomiting, and lethargy. In some cases, the symptoms can progress to include seizures, loss of consciousness and a coma. The severity of symptoms during ketoacidotic crises can vary. Between crises, individuals with SCOT deficiency have no symptoms. If the disease is properly treated with diet, normal growth and development are expected.

If the recommended diet is followed and precautions are taken during times of stress on the body such as illness, the long-term outlook for people affected by SCOT deficiency is good. With proper management, children with SCOT deficiency are expected to reach their developmental milestones at the appropriate age, and intellectual disability is not known to be associated with the disease. A good outcome is predicted even in individuals who have multiple ketoacidotic crises.