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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Medical Genetics

Diagnosis, Genetics, and Lab Results for CPT II Deficiency

At a Glance

CPT II deficiency is diagnosed through blood tests checking acylcarnitines and creatine kinase, along with CPT2 genetic sequencing. While newborn screening detects severe forms, it often misses the common myopathic form, making genetic testing the gold standard for a definitive diagnosis.

Diagnosing CPT II deficiency is often a journey of putting together a puzzle. Because the symptoms can come and go, doctors use a combination of family history, blood work during “crises,” and specialized genetic testing to confirm the diagnosis [1][2].

How CPT II Deficiency is Inherited

CPT II deficiency is an autosomal recessive disorder [3]. This means:

  • A person must inherit two changed (mutated) copies of the CPT2 gene—one from each parent—to have the condition [4].
  • The parents are usually carriers. They have one mutated copy and one working copy. Carriers typically do not have any symptoms because their one working gene provides enough enzyme for the body to function normally [4][5].
  • When two carriers have a child, there is a 25% chance the child will have CPT II deficiency, a 50% chance the child will be a carrier, and a 25% chance the child will be completely unaffected [4].
  • If you have the disease: You have two mutated genes. This means you will pass one mutated gene to every child you have, meaning all your children will be at least carriers. Your partner should consider carrier screening to fully understand the risks [4].

Newborn Screening and Its Limits

Most babies in many countries are screened for CPT II at birth using a blood spot test called an acylcarnitine profile [6][7].

  • The Goal: To find the severe infantile or neonatal forms early so treatment can start immediately [8].
  • The Limitation: This screening is not perfect. It often misses the myopathic form (the most common type), which may not show any signs until later in childhood or adulthood [9][7]. A “normal” newborn screen does not completely rule out the possibility of having the myopathic form of CPT II [10][11].

Lab Markers to Watch

When a doctor suspects CPT II deficiency, they look for specific “biochemical fingerprints” in the blood:

  • Acylcarnitines (C16 and C18:1): During a crisis, the body struggles to process long-chain fats, causing levels of these specific fats to build up in the blood [7][12].
  • Creatine Kinase (CK): This is an enzyme found in your muscles. When muscle tissue breaks down (rhabdomyolysis), CK levels skyrocket [12][13]. While CK might be normal between episodes, it is a critical marker during a crisis [3].
  • Blood Sugar and Ammonia: In severe infantile forms, doctors may also see low blood sugar (hypoglycemia) or high ammonia levels [4][14].

Genetic Testing: The “Gold Standard”

While blood tests provide clues, CPT2 gene sequencing is the only way to confirm the diagnosis definitively [10][1]. This test looks directly at the DNA to find the specific mutations.

One of the most common mutations is p.Ser113Leu (often called S113L) [15]. This specific mutation is fascinating and important for patients to understand:

  • Thermal Instability: In people with the S113L mutation, the CPT II enzyme works fairly well at a normal body temperature. However, if the body temperature rises—such as during a fever—the enzyme becomes unstable and stops working correctly [16][17].
  • This explains why a simple fever from a cold can trigger a major muscle crisis for some patients [16][18].

Knowing your specific mutation helps your medical team predict your “triggers” and create a more personalized care plan [1][19].

Common questions in this guide

How is CPT II deficiency inherited?
CPT II deficiency is an autosomal recessive disorder. This means a person must inherit two mutated copies of the CPT2 gene, one from each parent, to develop the condition.
Can newborn screening detect CPT II deficiency?
Newborn screening can detect the severe infantile or neonatal forms of the disease using an acylcarnitine profile. However, it often misses the more common myopathic form, which may not show signs until later in life.
What does the p.Ser113Leu (S113L) mutation mean?
The S113L mutation is a specific change in the CPT2 gene that makes the CPT II enzyme thermally unstable. This means the enzyme works normally at regular body temperatures but stops working during a fever, which can trigger a muscle crisis.
What is Creatine Kinase (CK) and why is it tested?
Creatine kinase is an enzyme found in your muscles. Doctors monitor CK levels because they skyrocket when muscle tissue breaks down during a CPT II deficiency crisis, helping to confirm and monitor a severe episode.
Why do family members need genetic testing if they have no symptoms?
Family members, such as parents of an affected child, are usually carriers with one working gene and one mutated gene. While carriers rarely have symptoms, testing helps them understand the risk of passing the condition to future children.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What specific mutations were found in my/my child's CPT2 gene sequencing report?
  2. 2.Does the mutation identified (like p.Ser113Leu) explain why a fever might trigger a crisis?
  3. 3.If the newborn screening was normal, why are we now suspecting CPT II deficiency?
  4. 4.What are our specific 'baseline' CK levels versus what you would expect to see during a crisis?
  5. 5.Is genetic counseling available to help us understand the recurrence risk for future pregnancies or the risks for family members?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (19)
  1. 1

    Recurrent rhabdomyolysis caused by palmitoyltransferase II (CPT-2) deficiency but complete normal acylcarnitine profile: A patient presentation and review of the literature.

    Lu CH, Yang CF, Chen YR, et al.

    Molecular genetics and metabolism reports 2024; (41()):101151 doi:10.1016/j.ymgmr.2024.101151.

    PMID: 39429887
  2. 2

    Cause of recurrent rhabdomyolysis, carnitine palmitoyltransferase II deficiency and novel pathogenic mutation.

    Çakar NE, Gör Z, Yeşil G

    Ideggyogyaszati szemle 2021; (74(3-4)):135-138 doi:10.18071/isz.74.0135.

    PMID: 33938664
  3. 3

    Carnitine palmitoyltransferase-II deficiency: case presentation and review of the literature.

    Mccormick BJ, Chirila RM

    Romanian journal of internal medicine = Revue roumaine de medecine interne 2021; (59(4)):420-424 doi:10.2478/rjim-2021-0021.

    PMID: 34118800
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    Carnitine palmitoyltransferase II (CPT II) deficiency responsible for refractory cardiac arrhythmias, acute multiorgan failure and early fatal outcome.

    Serra G, Antona V, Insinga V, et al.

    Italian journal of pediatrics 2024; (50(1)):67 doi:10.1186/s13052-024-01632-x.

    PMID: 38616285
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    Autosomal recessive frameshift variant broadens HECW2-related disease spectrum.

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    European journal of medical genetics 2025; (77()):105036 doi:10.1016/j.ejmg.2025.105036.

    PMID: 40812465
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    Detection of Early Onset Carnitine Palmitoyltransferase II Deficiency by Newborn Screening: Should CPT II Deficiency Be a Primary Disease Target?

    Mador-House R, Liu Z, Dyack S

    International journal of neonatal screening 2021; (7(3)) doi:10.3390/ijns7030055.

    PMID: 34449523
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    Carnitine palmitoyltransferase II deficiency with a focus on newborn screening.

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    Journal of human genetics 2019; (64(2)):87-98 doi:10.1038/s10038-018-0530-z.

    PMID: 30514913
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    Clinical characteristics and genetic analysis of six children with carnitine palmitoyltransferase 2 deficiency.

    Zhang Y, Qiu W, Zhang H, et al.

    Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 2024; (53(2)):207-212 doi:10.3724/zdxbyxb-2023-0611.

    PMID: 38650450
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    Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency.

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    Severe rhabdomyolysis in an infant due to fatty acid oxidation disorder: a case report.

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    Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity.

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    International journal of neonatal screening 2023; (9(4)) doi:10.3390/ijns9040062.

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    Carnitine palmitoyltransferase II deficiency and post-COVID vaccination rhabdomyolysis.

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    Carnitine Palmitoyltransferase II Deficiency (CPT II) Followed By Rhabdomyolysis and Acute Kidney Injury.

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    Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity.

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    Severe rhabdomyolysis in homozygote carnitine palmitoyltransferase II deficiency.

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    Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features.

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This page explains diagnostic tests and genetics for CPT II deficiency for educational purposes. Always consult a genetic counselor or your doctor to interpret your specific lab and genetic results.

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