What are the other Names for this Condition? (Also known as/Synonyms)

• 2-Methyl-3-Hydroxybutyricacidemia
• 3-Oxothiolase Deficiency Disorder
• Mitochondrial Acetoacetyl-CoA Thiolase Deficiency Disorder

What is Beta-Ketothiolase Deficiency Disorder? (Definition/Background Information)

• Beta-Ketothiolase Deficiency Disorder is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. This condition also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats
• Signs and symptoms typically appear between the ages of 6 and 24 months. Affected children experience intermittent episodes of ketoacidosis, characterized by vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and occasionally, seizures. In severe cases, these episodes can lead to coma
• Metabolic stroke is another finding that has been increasingly reported in children with this condition. Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein-rich foods
• Beta-Ketothiolase Deficiency Disorder is inherited in an autosomal recessive fashion and is caused by pathogenic variants (mutations) in the ACAT1 gene
• Treatment involves managing acute crises with intravenous (IV) fluids, glucose, and electrolytes along with bicarbonate
• Long-term management involves eating frequently, following a reduced-protein diet, avoidance of high-fat foods, and, in some cases, carnitine supplementation

(Source: Beta-Ketothiolase Deficiency Disorder; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Beta-Ketothiolase Deficiency Disorder? (Age and Sex Distribution)

• Beta-Ketothiolase Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur during infancy and early childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Beta-Ketothiolase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Beta-Ketothiolase Deficiency Disorder is an inherited condition
• Currently, no other risk factors have been clearly identified for this deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Beta-Ketothiolase Deficiency Disorder? (Etiology)

• Beta-Ketothiolase Deficiency Disorder is inherited in an autosomal recessive fashion and is caused by pathogenic variants (mutations) in the ACAT1 gene

(Source: Beta-Ketothiolase Deficiency Disorder; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Beta-Ketothiolase Deficiency Disorder?

The signs and symptoms of Beta-Ketothiolase Deficiency Disorder typically appear between the ages of 6 and 24 months.

• Affected children experience intermittent episodes of ketoacidosis, characterized by vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and occasionally, seizures. In severe cases, these episodes can lead to coma
• Metabolic stroke is another finding that has been increasingly reported in children with this condition
• Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein-rich foods

The signs and symptoms of Beta-Ketothiolase Deficiency Disorder may include:

• Dehydration
• Episodic ketoacidosis
• Intellectual disability
• Vomiting

(Source: Beta-Ketothiolase Deficiency Disorder; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Beta-Ketothiolase Deficiency Disorder Diagnosed?

Beta-Ketothiolase Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Beta-Ketothiolase Deficiency Disorder?

The complications of Beta-Ketothiolase Deficiency Disorder may include:

• Coma, when the disorder is severe
• Severe neurological complications due to metabolic stroke

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Beta-Ketothiolase Deficiency Disorder Treated?

• The treatment of Beta-Ketothiolase Deficiency Disorder involves managing acute crises with intravenous (IV) fluids, glucose, and electrolytes along with bicarbonate
• Long-term management involves eating frequently, following a reduced-protein diet, avoidance of high-fat foods, and, in some cases, carnitine supplementation

(Source: Beta-Ketothiolase Deficiency Disorder; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Beta-Ketothiolase Deficiency Disorder be Prevented?

Currently, Beta-Ketothiolase Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Beta-Ketothiolase Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Beta-Ketothiolase Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Beta-Ketothiolase Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/