CPT1 Deficiency

Other Names

Carnitine palmitoyl transferase deficiency, type 1A (CPT 1)

Carnitine palmitoyl transferase 1 deficiency

CPT1A

CPT 1 liver

Diagnosis Coding

E71.314, muscle carnitine palmitoyltransferase deficiency

Disorder Category

A fatty acid oxidation disorder

Screening

Finding

Elevated C0 and C0/(C16+C18) ration

Tested By

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

Overview

Carnitine palmitoyl transferase 1A (CPT1) is a mitochondrial enzyme involved in the conjugation of fatty acids to carnitine for subsequent transfer inside mitochondria through the action of a translocase. Mutations in the CPT1A gene cause CPT1. Deficiency of CPT1 results in impaired energy production, usually manifest during periods of prolonged fasting and/or increased energy demands (fever, stress), resulting in rapid onset of hypoglycemic crises. CPT1A is predominantly expressed in the liver and the muscle and the heart are not primarily affected in this condition.

Prevalence

CPT 1 is rare [Schulze: 2003], with fewer than 40 known cases. [CPT1 Deficiency (GeneReviews)]

Inheritance

Autosomal recessive

Prenatal Testing

DNA testing possible 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

With treatment, episodes of hypoglycemia, and consequent neurologic injury, may be avoided. Without treatment, injury from hypoglycemic episodes may lead to developmental delay, seizures, coma, and death. Acute fatty liver of pregnancy may occur in a heterozygous mother of a homozygous fetus.

Initial signs/symptoms typically begin suddenly in association with an illness between eight and eighteen months of life and may be life-threatening. They usually include:
  • poor appetite,
  • vomiting,
  • lethargy,
  • lab findings:
    • hyperammonemia,
    • elevated transaminases,
    • metabolic acidosis, and
    • hypoglycemia.

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, enzyme activity assay in cultured fibroblasts, CPT1A gene sequencing. The increased C0/(C16+C18) ratio is better detected from the dried blood spot collected for newborn screening. In plasma, C0 can be only mildly increased with low levels of C16 and C18.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need to avoid fasting and to seek urgent care when the infant becomes ill (see CPT1 Deficiency - Information for Parents (STAR-G) for additional information);
  • Provide a letter and, when old enough, a MedicAlert bracelet indicating the risk for hypoglycemia and need for urgent treatment with IV glucose when illness or stress lead to symptoms;
  • Frequent, low fat, and high carbohydrate meals and snacks and, for infants, cornstarch feedings at night as a slow-release carbohydrate source;
  • Medium Chain Triglyceride (MCT) oil supplements may be indicated for some children;
  • 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

CPT1 Deficiency - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

ACT Sheet for CPT1 Deficiency (ACMG) (PDF Document 344 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.

CPT1 Deficiency (GeneReviews)
Excellent review by Michael J Bennett, PhD, FRCPath, DABCC and Srinivas B Narayan, PhD, including clinical description, differential, management, genetic counseling, molecular genetics, and a bibliography.

Resources for CPT1 Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

CPT1 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.

CPT1 Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

United Mitochondrial Disease Foundation
The United Mitochondrial Disease Foundation site provides parents and providers with information over 40 mitochondrial diseases; definitions of medical terms; professional articles; chapter links; newsletters; event information; and links to other sites.

Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.

Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.

Services

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for CPT1 deficiency, last 15 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

Authors

Reviewing Authors: Kimberly Hart, MS, LCGC - 6/2012
Nicola Longo, MD, PhD - 3/2007
Content Last Updated: 6/2012

Page Bibliography

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