Carnitine-Acylcarnitine Translocase (CACT) Deficiency
Description
Clinical Characteristics
Without treatment, hypoglycemic crises lead to coma and death; cardiomyopathy and cardiac arrhythmia may also be fatal. The neonatal type, with essentially no CACT activity, is the most common type and comes with high morbidity and mortality. The childhood type, with some residual CACT activity, is milder and usually does not have cardiac involvement.
- Poor feeding
- Lethargy
- Weakness
- Hepatomegaly
- Cardiac insufficiency and/or arrhythmia
- Lab findings:
- Hyperammonemia
- Metabolic acidosis
- Hypoketotic hypoglycemia
- Elevated CK and liver enzymes
- Elevated C16 and/or C18:1 on acylcarnitines (most specific finding)
Incidence
Primary Care Management
Next Steps After a Positive Screen
- IMMEDIATELY contact the family to notify them of the positive screen and evaluate the infant for poor feeding, vomiting, lethargy, hepatomegaly, and cardiac insufficiency/arrhythmia (bradycardia, cardiac arrest).
- The following rapid lab tests can help determine severity: Glucose, electrolytes, blood gas, lactate, ammonia, liver function tests (LFTs), and creatine phosphokinase (CPK).
- Transport to hospital if there are seizures, hypoglycemia, liver dysfunction, or cardiac insufficiency. Provide information and support to the family.
- On the same day, contact Biochemical Genetics (Metabolics) (see NM providers [1]) and obtain confirmatory testing.
Confirming the Diagnosis
- To confirm the diagnosis of CACT deficiency, work with Newborn Screening Services (see NM providers [1]).
- Additional testing may include quantitative plasma acylcarnitine profile, urine organic acid analysis. Diagnosis is confirmed by enzyme activity assay in cultured fibroblasts or DNA sequencing of the SLC25A20 gene. Carnitine palmitoyl transferase 2 (CPT2) deficiency can have a similar clinical and biochemical presentation, making DNA testing necessary to differentiate the 2 conditions.
- Most cases will be identified soon after birth by Newborn Screening programs. Genetic testing is possible for at-risk family members if both disease-causing mutations of an affected family member have been previously identified.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) Clinics (see NM providers [1]).
- 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 maintenance of regularly scheduled nutritional intake and strict dietary limitation of long-chain fatty acids as guided by a metabolic dietitian.
- Treatment with medium-chain triglyceride (MCT) oil or triheptanoin as an additional energy source, as outlined by the metabolic team.
- Supplementation of carnitine and essential fatty acids may be indicated.
- For those identified after irreversible neurological sequelae, assist in management, particularly with developmental and educational services.
Resources
Information & Support
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.
For Professionals
CACT Deficiency (GARD)
Compilation of information, articles, research, case studies, and genetics; Genetic and Rare Diseases from the National Institute
of Health.
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
For Parents and Patients
Support
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 (MedlinePlus)
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.
Tools
Confirmatory Algorithms for Elevated C16 and/or C18:1 Acylcarnitine (ACMG) ( 162 KB)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American
College of Medical Genetics.
NM ACT Sheet for CPT II/CACT Deficiencies (ACMG) ( 121 KB)
Provides recommendations for clinical and laboratory follow-up of the newborn with out-of-range screening results, along with
national and local resources for clinicians and families; American College of Medical Genetics.
Services for Patients & Families in New Mexico (NM)
Service Categories | # of providers* in: | NM | NW | Other states (4) (show) | | MT | NV | RI | UT |
---|---|---|---|---|---|---|---|---|---|
Biochemical Genetics (Metabolics) | 1 | 1 | 2 | 2 | 3 | 3 | |||
Biochemical Genetics (Metabolics) Clinics | 1 | 1 | 2 | 2 | 1 | 3 | |||
Medical Genetics | 4 | 1 | 8 | 5 | 4 | 6 | |||
Newborn Screening Services | 1 | 1 | 4 | 2 | 2 | 3 |
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.
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
Mahapatra S, Ananth A, Baugh N, Damian M, Enns GM.
Triheptanoin: A Rescue Therapy for Cardiogenic Shock in Carnitine-acylcarnitine Translocase Deficiency.
JIMD Rep.
2018;39:19-23.
PubMed abstract / Full Text
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
Yan HM, Hu H, Ahmed A, Feng BB, Liu J, Jia ZJ, Wang H.
Carnitine-acylcarnitine translocase deficiency with c.199-10 T>G and novel c.1A>G mutation: Two case reports and brief literature
review.
Medicine (Baltimore).
2017;96(45):e8549.
PubMed abstract / Full Text