Home > Newborn Disorders > CACT deficiency
CACT deficiency
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.98% [Schulze: 2003]Names
CACT deficiency
Carnitine acylcarnitine translocase (CACT or CAT) deficiency
Carnitine acylcarnitine carrier (CAC) deficiency
Solute carrier family 25 member 20 (SLCA25A20)
Overview
Caused by a deficiency of CACT, a mitochondrial membrane carrier protein, responsible for transport of fatty acids 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 are unavailable for mitochondrial oxidation, production of ATP, and acetyl-CoA, and resultant energy production and gluconeogenesis. Long-chain acylcarnitines and free fatty acids can alter the electrical properties of cardiac cells resulting in arrhythmia.Prevalence
about 1/250,000 live births [Schulze: 2003]Maternal and Family History
There may be a family history of Sudden Infant Death Syndrome (SIDS). Maternal preeclampsia has been reported.Prenatal Testing
DNA testing, enzyme testing, acylcarnitine analysis, and protein analysis by amniocentesis or CVS.Clinical Characteristics
With treatment with medium chain triglycerides that do not require carnitine to enter the mitochondria, mild forms of the disease respond. [Iacobazzi: 2004] The disease may be fatal. 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;
- vomiting;
- lethargy;
- weakness;
- hepatomegaly;
- cardiac insufficiency or arrythmia;
- lab findings;
- hyperammonemia;
- metabolic acidosis;
- hypoketotic hypoglycemia; and
- mildly elevated CK and liver enzymes.
Follow-up on positive screening test
Quantitative plasma acylcarnitine profile, urine organic acid analysis. Diagnosis is confirmed by enzyme assay in fibroblasts or DNA sequencing.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, hepatomegaly, cardiac insufficiency or arrythmia (bradycardia);
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-581-8943); See also Services below;
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 info 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 Management
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.Resources
Information & Support
For Professionals
CACT deficiency info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
ACT Sheet for Elevated C16 and/or C18:1 Acylcarnitine (ACMG)
(
345 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Resources for CACT deficiency (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
CACT deficiency (OMIM)
Extensive review of the literature, including clinical features and genetics, from the Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE,
and links to other scientific information and sites.
National Newborn Screening & Genetics Resource Center
Provides information for families and professionals about genetic screening; links to support and advocacy groups; links to
state genetic contacts; newsletters; fact sheets; data reports; publications; and more.
For Parents and Patients
CACT deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about CACT and
links to other sites including parent support groups.
CACT deficiency (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Fatty Oxidation Disorders (FOD) Family Support Group
The FODsupport.org site offers a variety of information for families about fatty acid oxidation disorders, support groups,
coping, finances, and links to other sites.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for review articles on CACT deficiency in the last 5 years.
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 3/2007 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 3/2008 |
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