CACT: Carnitine Acylcarnitine Translocase Deficiency

Carnitine acylcarnitine translocase deficiency is a type of genetic condition where the enzyme that helps move long-chain fats into the mitochondria to be broken down is unable to function properly. This prevents the body from creating needed energy during times of stress, illness, fasting, and exercise, which can lead to medical symptoms. The body usually gets its energy by breaking down, or burning, fats and sugars. People with FAODs cannot properly break down certain types of fats.

CACT Deficiency

SLC25A20

• Autosomal recessive

People usually have two copies of the SLC25A20 gene, one inherited from each parent. CACT deficiency occurs when there are changes in both copies of the SLC25A20 gene (autosomal recessive inheritance). Someone who has a change in only one copy of the SLC25A20 gene is called a carrier, and they usually do not have any medical symptoms. If both parents are carriers, there is a 1 in 4 chance with each pregnancy that their child will have CACT deficiency.

The exact frequency of CACT deficiency is unknown, but it is thought to be very rare. Scientific papers have reported less than 60 known cases of CACT deficiency worldwide.

Both Male and Female

CACT deficiency can cause a range of signs and symptoms. Whether your child was diagnosed via newborn screening may also affect when, if, and how these symptoms present. Always check with your doctor if your child is doing something out of “their” normal, as every child may present with symptoms a little differently.

Signs and symptoms may include:

• Extreme tiredness or fatigue (lethargy)
• Irritability
• Difficulty walking
• High ammonia levels in the blood (hyperammonemia)
• Enlarged liver (hepatomegaly)
• Enlarged, weakened heart (cardiomyopathy)
• Abnormal heart rhythms (arrhythmias)
• Total failure of heart and lung function
• Life threatening low blood sugar with lack of ketones (hypoketotic hypoglycemia)

Milder forms of CACT deficiency may be identified with future research.

CACT deficiency can be diagnosed by:

• Measuring biochemical markers in the blood or urine (acylcarnitine analysis and organic acid analysis)
• Measuring the amount of CACT activity in the blood or skin cells
• Performing a genetic test to look for changes in the SLC25A20 gene

Yes

Treatment and management of CACT deficiency may include:

• Regular eating schedules to prevent of low blood sugar (hypoglycemia)
• Possible nutritional supplements like medium-chain triglycerides (MCT oil)
• Possible carnitine supplements (Carnitor) based on protein activity and free carnitine levels
• Continuous feeding directly into the stomach in extreme cases
• Intravenous (IV) sugar-containing fluids called D10 during metabolic crisis
• Dialysis if blood ammonia does not reverse when low blood sugar is corrected

Parents should call their healthcare provider immediately if babies show symptoms like excessive sleepiness, vomiting, diarrhea, a fever, poor appetite, or an infection. Medical treatment should be sought immediately if there is loss of consciousness or severe confusion (decompensation), as these are signs of dangerously low blood sugar.

Patients should discuss the appropriate preparation for anesthesia with their metabolic team.

• Carnitine-acylcarnitine translocase deficiency – About the Disease – The National Institutes of Health
• CACT Deficiency | Fatty Acid Oxidation Disorders Diagnosis – The INFORM Network
• Vatanavicharn N, et al. Carnitine-acylcarnitine translocase deficiency: Two neonatal cases with common splicing mutation and in vitro bezafibrate response. Brain Dev. 2015 Aug;37(7):698-703. 

Connecting with others impacted by a rare disease allows for vital information to be shared about day-to-day life, prevents isolation, and gives hope. Please contact MitoAction for peer support opportunities at 888-MITO-411 or email mito411@mitoaction.org.

Other resources we recommend are:

• New Patient Kit for Mitochondrial Conditions
• Planning and Preparation
• Monthly Expert Series
• Energy in Action Podcast