Carnitine Palmitoyltransferase II Deficiency via the CPT2 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
869 CPT2$680.00 81404 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Clinical sensitivity of this test is expected to be high for patients with confirmed carnitine palmitoyltransferase II deficiency as, to date, nearly all reported patients have had two pathogenic variants detectable via direct CPT2 sequencing. Based on combined results from several studies, 296 alleles have been reported in 154 patients, for a sensitivity of ~96% (Deschauer et al. 2005; Corti et al. 2008; Isackson et al. 2008; Fanin et al. 2012; Joshi et al. 2014).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 CPT2$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

To date, no gross deletions or duplications have been reported in the CPT2 gene (Human Gene Mutation Database). Therefore, the sensitivity of duplication/deletion testing for this rare disorder, although not precisely known, is low.

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Clinical Features

Carnitine palmitoyltransferase II (CPT II) deficiency is one of the most commonly inherited disorders of long-chain fatty acid oxidation (Corti et al. 2008). Three types of CPT II deficiency have been reported.

CPT II deficiency Types I and II are rare, severe disorders that involve multiple body systems. Patients present with recurrent attacks of acute liver failure with hypoketotic hypoglycemia, respiratory distress, lethargy, vomiting, seizures, transient hepatomegaly, and possibly coma. Cardiac involvement, including cardiomyopathy and cardiac arrhythmias that can lead to sudden death, is observed in about half of the affected patients. These forms of CPT II deficiency are associated with enzyme activity levels <10% of control. Biochemically, patients may be observed to have low levels of free and total carnitine, metabolic acidosis, and hyperammonemia.

Type II is classified as severe infantile CPT II deficiency, and is also referred to as the hepatocardiomuscular form. Onset for Type II patients is typically within the first year of life, with fatality being most common during the time period from ~3-18 months of age (Illsinger et al. 2008).

Type I CPT II deficiency is classified as the lethal neonatal form and presents within the first few days of life. In addition to the clinical features observed in type II patients, type I CPT II deficient patients are typically observed to have dysmorphic features, such as facial abnormalities and malformations of the kidneys and brain (Bonnefont et al. 2004; Corti et al. 2008; Wieser 2017).

Type III CPT II deficiency is the most common. This form is primarily a myopathic disorder. Onset occurs from childhood through late adulthood, though is most commonly observed between the ages of 6 and 20 years (Bonnefont et al. 2004). Symptoms include episodic attacks of myalgia and muscle stiffness or weakness, rhabdomyolysis and myoglobinuria. Creatine kinase (CK) and transaminase levels may be elevated during attacks, while carnitine levels may be decreased or normal. Muscle lipid storage has been observed in approximately 20% of patients. A variety of stressors may trigger an attack, such as prolonged exercise, fasting, exposure to extreme temperatures, viral infection, fever, emotional stress, or exposure to anesthesia or other drugs. Between attacks, patients are typically clinically normal. For reasons that are not understood, males are much more likely to be affected than females (Bonnefont et al. 2004; Corti et al. 2008; Wieser 2017).

Laboratory analysis in affected patients may reveal elevated C12 to C18 acylcarnitines, especially C16 and C18:1. Patients with glutaric aciduria type II and carnitine-acylcarnitine translocase deficiency may also have a similar acylcarnitine profile, though other biochemical abnormalities may help to differentiate between these disorders (Wieser 2017).


CPT II deficiency is primarily an autosomal recessive disorder, although a few manifesting heterozygotes have been reported (Wieser 2017). The CPT2 gene is the only gene that is known to be involved. Approximately 100 pathogenic variants in the CPT2 gene have been reported to date. Approximately two-thirds of the pathogenic variants are missense, with the remainder being small frameshift deletions, insertions and splice variants (Anichini et al. 2011; Human Gene Mutation Database).

Several variants have been commonly reported to be associated with the myopathic form (type III) of CPT II deficiency: p.Ser113Leu (accounts for ~60-70% of alleles in Caucasians), p.Lys414Thrfs*7 (~20%), p.Pro50His, p.Arg503Cys, p.Gly549Asp, and p.Met214Thr (~15% together) (Deschauer et al. 2005; Fanin et al. 2012; Joshi et al. 2014; Wieser 2017). In general, the severe infantile and lethal neonatal forms are associated with variants expected to have a severe effect on the protein, such as p.Lys414Thrfs*7 (Wieser 2017). It has been noted that for most patients with the myopathic form, at least one pathogenic variant resides within exons 1 through 3, whereas patients with the infantile or neonatal forms typically have two pathogenic variants located in exons 4 or 5 (Bonnefont et al. 2004). There is some level of genotype-phenotype correlation, with myopathic patients typically carrying variants that have a less severe effect on the CPT II protein, while patients with the infantile or neonatal forms usually have at least one severe, null variant (Corti et al. 2008; Isackson et al. 2008). However, this is not always the case, as some variants have been observed in patients with different types of CPT II deficiency, such as p.Lys414Thrfs*7 (Wieser 2017).

The carnitine palmitoyltransferase system is a set of proteins with enzyme and transporter functions. These proteins are involved in long-chain fatty acid (LCFA) metabolism, being specifically responsible for the net transport of LCFAs from the cytosol into the mitochondrial matrix. The CPT II protein is located within the mitochondrial matrix where it is associated with the inner mitochondrial membrane. The CPT II protein converts acyl-carnitines that were transported into the mitochondrial matrix back to acyl-CoA molecules, which are then available for β-oxidation (Bonnefont et al. 2004).

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of all coding exons of the CPT2 gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known pathogenic variants or to confirm research results.

Indications for Test

Patients with clinical and biochemical test results consistent with CPT II deficiency are good candidates for this test. Family members of patients who have known CPT2 pathogenic variants are also good candidates. We will also sequence the CPT2 gene to determine carrier status.


Official Gene Symbol OMIM ID
CPT2 600650
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Metabolic Myopathies, Rhabdomyolysis and Exercise Intolerance Sequencing Panel


Genetic Counselors
  • Anichini A. et al. 2011. Neurological Research. 33: 24-32. PubMed ID: 20810031
  • Bonnefont J.P. et al. 2004. Molecular Aspects of Medicine. 25: 495-520. PubMed ID: 15363638
  • Corti S. et al. 2008. Journal of the Neurological Sciences. 266: 97-103. PubMed ID: 17936304
  • Deschauer M. et al. 2005. Archives of Neurology. 62: 37-41. PubMed ID: 15642848
  • Fanin M. et al. 2012. Clinical Genetics. 82: 232-9. PubMed ID: 21913903
  • Human Gene Mutation Database (Bio-base).
  • Illsinger S. et al. 2008. American Journal of Medical Genetics. Part A. 146A: 2925-8. PubMed ID: 18925671
  • Isackson P.J. et al. 2008. Molecular Genetics and Metabolism. 94: 422-7. PubMed ID: 18550408
  • Joshi P.R. et al. 2014. Journal of the Neurological Sciences. 338: 107-11. PubMed ID: 24398345
  • Wieser T. 2017. Carnitine Palmitoyltransferase II Deficiency. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301431
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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