CACT & CPT II Deficiencies

Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

Carnitine acylcarnitine carrier (CAC) deficiency
Carnitine acylcarnitine translocase (CACT or CAT) deficiency
Carnitine palmitoyltransferase 2 (CPT 2) deficiency
Solute carrier family 25 member 20 (SLC25A20) deficiency

ICD-10 Coding

E71.318, Other disorders of fatty-acid oxidation

Disorder Category

Fatty acid oxidation disorder

Screening

Abnormal Finding

Elevated C16 and/or C18:1 (acylcarnitines)

Tested By

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

Description

Genetic mutations can cause deficiencies in carnitine-acylcarnitine translocase (CACT) or carnitine palmitoyltransferase II (CPT II). CACT and CPT II are mitochondrial membrane carrier proteins responsible for transporting long-chain acylcarnitines into the mitochondria for fatty acid oxidation. Without either of these transporters, these long-chain acylcarnitines cannot be properly metabolized by the mitochondria, causing insufficient energy production. During prolonged fasting and/or periods of increased energy demands (fever, stress), energy production relies increasingly on fatty acid oxidation. This process is particularly important in fatty acid-dependent tissues like the heart, liver, and skeletal muscles.
  • CACT deficiency most commonly presents shortly after birth with hypoketotic hypoglycemia, hyperammonemia, liver dysfunction, and cardiac arrest and generally has a very poor prognosis despite early intervention except in the few reported mild cases.
  • CPT II deficiency has a much more variable presentation that can range from lethal neonatal, with a similar presentation as CACT deficiency, to the much milder and far more common myopathic form presenting with exercise-induced muscle pains and myoglobinuria in adolescence or adulthood. [MedlinePlus: 2022]

Clinical Characteristics

With treatment, mild to moderate forms of these disorders generally respond well with significantly reduced morbidity and mortality. In particular, for myopathic CPT II deficiency, there is expected normal growth, development, and lifespan. However, with more severe cases, affected newborns will become symptomatic well before newborn screening results can return. Currently, available therapies may not be enough to allow for survival beyond infancy. Treatment directed by a Biochemical (Metabolic) Geneticist consists of avoidance of fasting, a modified diet low in long-chain fatty acids, and supplementation with medium-chain fatty acids or triheptanoin.

Without treatment, moderate to severe cases will continue to experience severe episodic hypoglycemic crises, liver disease, cardiomyopathy, and cardiac arrhythmias that could ultimately lead to cardiac arrest, coma, and death. Mild myopathic CPT II deficient patients are the exception and may not experience clinically noticeable symptomology until adolescence/adulthood with recurrent muscle pains that may give way to severe episodes of rhabdomyolysis.

Incidence

CACT deficiency occurs in approximately 1:250,000 live births [Schulze: 2003] and 1:60,000 in some Asian populations. [Yan: 2017] CPT II deficiency is also rare though the exact incidence is unknown.

Inheritance

Autosomal recessive

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). Elicit any history of sudden unexpected death in a sibling.
  • Transport to the hospital if there are seizures, hypoglycemia, liver dysfunction, or cardiac insufficiency. Provide information and support to the family.
  • The following rapid lab tests can help determine severity: Glucose, electrolytes, blood gas, lactate, ammonia, liver function tests (LFTs), and creatine phosphokinase (CPK). Additional testing may include quantitative plasma acylcarnitine profile and urine organic acid analysis.
  • On the same day, contact Newborn Screening Services (see NM providers [3]) and Biochemical Genetics (Metabolics) (see NM providers [1]) and obtain confirmatory testing.

Confirming the Diagnosis

If the Diagnosis is Confirmed

  • For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) (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 specialist.
  • For those identified after irreversible neurological sequelae, assist in management, particularly with developmental and educational services.

Resources

Information & Support

Related Portal Content
After a Diagnosis or Problem is Identified
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

Carnitine Palmitoyltransferase II Deficiency (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library 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.

Carnitine Palmitoyltransferase II Deficiency (MedLinePlus)
Description, frequency, causes, inheritance, and Resources; 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

NM ACT Sheet for CPT II/CACT Deficiencies (ACMG) (PDF Document 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.

Confirmatory Algorithms for Elevated C16 and/or C18:1 Acylcarnitine (ACMG) (PDF Document 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.

Services for Patients & Families in New Mexico (NM)

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.

Authors & Reviewers

Initial publication: March 2007; last update/revision: May 2022
Current Authors and Reviewers:
Author: Brian J. Shayota, MD, MPH
Contributing Author: Jennifer Goldman, MD, MRP, FAAP
Reviewer: Nancy C. Rose, MD
Authoring history
2021: update: Brian J. Shayota, MD, MPHA
2012: update: Kimberly Hart, MS, LCGCA; Lynne M. Kerr, MD, PhDA
2007: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

MedlinePlus.
Carnitine palmitoyltransferase II deficiency.
National Library of Medicine; (2022) https://medlineplus.gov/genetics/condition/carnitine-palmitoyltransfer.... Accessed on May 12, 2022.

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