CACT Deficiency

Other Names

Carnitine acylcarnitine translocase (CACT or CAT) deficiency

Carnitine acylcarnitine carrier (CAC) deficiency

Solute carrier family 25 member 20 (SLCA25A20) deficiency

Diagnosis Coding

E71.318, other disorders of fatty-acid oxidation

Disorder Category

A fatty acid oxidation disorder



Elevated C16 and/or C18:1 (acylcarnitines)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.98% [Schulze: 2003]


Mutations in the SLC25A20 gene cause carnitine-acylcarnitine translocase (CACT) deficiency. CACT is a mitochondrial membrane carrier protein, responsible for transport of long-chain fatty acids conjugated with carnitine into mitochondria for oxidation. During prolonged fasting and/or periods of increased energy demands (fever, stress) energy production relies increasingly on fatty acid oxidation. Without CACT, long-chain acylcarnitines cannot enter mitochondrial to undergo subsequent oxidation, production of ATP, and acetyl-CoA, with resultant energy production. Long-chain acylcarnitines and free fatty acids can alter the electrical properties of cardiac cells resulting in arrhythmia. Patients with the most severe forms (the most frequent) present shortly after birth with hypoglycemia and cardiac arrest, independently from fasting or any other stressor beyond the normal birth process.


Approximately1 in 250,000 live births [Schulze: 2003]


Autosomal recessive

Maternal & Family History

There may be a family history of sudden infant death syndrome (SIDS). Maternal preeclampsia has been reported.

Prenatal Testing

DNA testing by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

Clinical Characteristics

Treatment with medium chain triglycerides that do not require carnitine to enter the mitochondria, mild and severe forms of the disease may respond, [Iacobazzi: 2004] although the disease may be fatal or leave irreversible brain damage. The results of newborn screening can return after the infant is already symptomatic. Without treatment, hypoglycemic crises lead to coma and death; cardiomyopathy and cardiac arrhythmia may also be fatal. The neonatal type, with essentially no CACT and poor outcomes, is more common; the childhood type, with some residual CACT activity, is milder and usually does not have cardiac involvement.

Initial symptoms/signs may include:
  • poor feeding
  • lethargy
  • weakness
  • hepatomegaly
  • cardiac insufficiency and/or arrhythmia
  • lab findings:
    • hyperammonemia
    • metabolic acidosis
    • hypoketotic hypoglycemia
    • elevated CK and liver enzymes

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, urine organic acid analysis. Diagnosis is confirmed by enzyme activity assay in cultured fibroblasts or DNA sequencing. Carnitine palmitoyl transferase 2 (CPT2) deficiency causes the same pattern of abnormal acylcarnitines and DNA testing is the easiest way to differentiate the two conditions.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see CACT Deficiency - Information for Parents (STAR-G) for additional information);
  • Support initiation and maintenance of dietary restriction of long chain fatty acids, high carbohydrate/low-fat diet, avoidance of fasting;
  • Carnitine supplements, medium chain triglyceride (MCT) oil supplements, and cornstarch may be indicated;
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.


Information & Support

For Professionals

CACT Deficiency - Informaion for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

Resources for CACT Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

CACT Deficiency (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

CACT Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

CACT Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.


ACT Sheet for Elevated C16 and/or C18:1 Acylcarnitine (ACMG) (PDF Document 345 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.


Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

PubMed search for CACT deficiency, last 5 years.

Longo N, Amat di San Filippo C, Pasquali M.
Disorders of carnitine transport and the carnitine cycle.
Am J Med Genet C Semin Med Genet. 2006;142C(2):77-85. PubMed abstract / Full Text


Reviewing Authors: Kimberly Hart, MS, LCGC - 6/2012
Nicola Longo, MD, PhD - 3/2007
Compiled and edited by: Alfred Romeo, RN, PhD - 3/2007
Content Last Updated: 6/2012

Page Bibliography

Iacobazzi V, Pasquali M, Singh R, Matern D, Rinaldo P, Amat di San Filippo C, Palmieri F, Longo N.
Response to therapy in carnitine/acylcarnitine translocase (CACT) deficiency due to a novel missense mutation.
Am J Med Genet A. 2004;126(2):150-5. PubMed abstract

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract