CACT Deficiency
Other Names
Carnitine acylcarnitine translocase (CACT or CAT) deficiency
Carnitine acylcarnitine carrier (CAC) deficiency
Solute carrier family 25 member 20 (SLCA25A20) deficiency
Screening
Tested By
Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.98% [Schulze: 2003]Overview
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.Incidence
Approximately1 in 250,000 live births [Schulze: 2003]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
- Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, hepatomegaly, cardiac insufficiency or arrhythmia (bradycardia, cardiac arrest);
- To confirm the diagnosis, work with the following service(s): Newborn Screening Services (see RI providers [1]);
- For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Genetics (see RI providers [4]);
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.Resources
Information & Support
For Professionals
Resources for CACT Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.
CACT Deficiency (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; 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.
Carnitine-acylcarnitine translocase deficiency (MedlinePlus)
Excellent, detailed review of condition for patients and families; National Library of Medicine and National Institutes of
Health.
Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.
Tools
ACT Sheet for Elevated C16 and/or C18:1 Acylcarnitine (ACMG) (
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.
Services for Patients & Families in Rhode Island (RI)
| Service Categories | # of providers* in: | RI | NW | Other states (5) (show) | | ID | MT | NM | NV | UT |
|---|---|---|---|---|---|---|---|---|---|---|
| Newborn Screening Services | 1 | 1 | 22 | 4 | 2 | 2 | 3 | |||
| Pediatric Genetics | 4 | 1 | 3 | 7 | 4 | 5 | 7 | |||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Helpful Articles
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
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