Get Help in Rhode IslandCACT & CPT II Deficiencies
Guidance for primary care clinicians receiving a positive newborn screen result
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
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
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 RI providers [2]) and Biochemical Genetics (Metabolics) (see RI providers [3]) and obtain confirmatory testing.
Confirming the Diagnosis
- Most cases will be identified soon after birth by Newborn Screening programs. Work with Newborn Screening Services (see RI providers [2]) and Biochemical Genetics (Metabolics) (see RI providers [3]) to confirm the diagnosis using molecular genetic testing.
- 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) (see RI providers [3]).
- 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.
Tools
RI ACT Sheet for CPT II/CACT Deficiencies (ACMG) (
123 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) ( 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 Rhode Island (RI)
| Service Categories | # of providers* in: | RI | NW | Other states (3) (show) | | NM | NV | UT |
|---|---|---|---|---|---|---|---|---|
| Biochemical Genetics (Metabolics) | 3 | 1 | 1 | 2 | 2 | |||
| Medical Genetics | 4 | 1 | 2 | 5 | 7 | |||
| Newborn Screening Services | 2 | 1 | 3 | 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
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