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β-Ketothiolase Deficiency via the ACAT1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
ACAT1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9499ACAT181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Maxime Cadieux-Dion, PhD

Clinical Features and Genetics

Clinical Features

β-ketothiolase deficiency is an inborn error of ketone body metabolism that usually presents as intermittent ketoacidotic episodes. Onset of the first ketoacidotic episode is usually early in life; the median age is 15 months, with a range of 3 days to 48 months. Frequency of attacks tends to decrease or cease with age, making the consequences avoidable if diagnosed early and managed properly. Affected individuals are typically asymptomatic between episodes, but the extent of the clinical features varies based on the patient and the severity of the attack. Some of the first symptoms of an episode can be vomiting, lethargy, and fever. In about half of the affected patients, a severe attack is associated with unconsciousness/coma, which can result in subsequent intellectual disability or death (Fukao et al. 2001; Nakamura et al. 2001). Following an attack, some patients have also experienced severe headaches, developmental delay, basal ganglion abnormalities, dystonia, dilated cardiomyopathy, prolonged QT interval, neutropenia and thrombocytopenia (Mitchell and Fukao et al. 2014). β-ketothiolase deficient patients are usually identified after an attack through a urinary organic acid analysis, with results showing elevated excretion of the isoleucine catabolism intermediates 2-methyl-3-hydroxybutyrate, 2-methylacetoacetate, and tiglyglycine (Catanzano et. al. 2010; Fukao et al. 2010a; Akella et. al. 2014). These patients have also been known to have elevated levels of 2-methyl-3-hydroxybutyrylcarnitine (C5OH) and tiglylcarnitine (C5:1) in blood plasma (Catanzano et. al. 2010; Akella et. al. 2014).


β-ketothiolase deficiency is inherited in an autosomal recessive manner and is caused by variations in the ACAT1 gene, which is the only gene known to be involved. Approximately 70 different pathogenic variants have been identified to date, with approximately half of those being missense variants. The remainder are a mix of nonsense variants, splice site variants, and small insertions and deletions. Only two gross deletions and one tandem duplication of multiple exons have been identified at this time (Zhang et. al. 2006; Fukao et. al. 2007; Fukao et al. 2013; Human Gene Mutation Database). Pathogenic variants in the ACAT1 gene are heterogeneous and no common pathogenic variants have yet been identified.

Normally, the mitochondrial acetoacetyl-CoA thiolase (T2) enzyme catalyzes the processing of isoleucine. Pathogenic variants in the ACAT1 gene can greatly reduce or eliminate the activity of this enzyme, causing ketoacidosis and elevated isoleucine catabolism intermediates in the urine (Fukao et al. 2010a).

Clinical Sensitivity - Sequencing with CNV PGxome

Test sensitivity should be high in patients with clinical symptoms of β-ketothiolase deficiency. Fukao et al. (2001) reported 2 alleles in 100% of the 26 patients studied, and in a second study, they reported reported 2 alleles in 100% of the 10 patients studied (Fukao et al. 2010b). Sakurai et al. (2007) reported 2 alleles in 100% of the 6 patients studied.

Testing Strategy

This test provides full coverage of all coding exons of the ACAT1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients showing clinical features consistent with β-ketothiolase deficiency (ketoacidotic episodes, elevated excretion of isoleucine catabolism intermediates). Family members of patients who have known ACAT1 mutations are also good candidates. We will also sequence the ACAT1 gene to determine carrier status.


Official Gene Symbol OMIM ID
ACAT1 607809
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Alpha-Methylacetoacetic Aciduria AR 203750


  • Akella R.R. et al. 2014. Brain & Development. 36: 537-40. PubMed ID: 23958592
  • Catanzano F. et al. 2010. Journal of Inherited Metabolic Disease. 33 Suppl 3: S91-4. PubMed ID: 20157782
  • Fukao T. et al. 2001. Molecular Genetics and Metabolism. 72: 109-14. PubMed ID: 11161836
  • Fukao T. et al. 2007. Molecular Genetics and Metabolism. 92: 375-8. PubMed ID: 17719254
  • Fukao T. et al. 2010a. Molecular Genetics and Metabolism. 100: 339-44. PubMed ID: 20488739
  • Fukao T. et al. 2010b. Molecular Genetics and Metabolism. 100: 37-41. PubMed ID: 20156697
  • Fukao T. et al. 2013. Molecular Genetics and Metabolism. 110: 184-7. PubMed ID: 23920042
  • Human Gene Mutation Database (Bio-base).
  • Mitchell G.A. and Fukao T. 2014. Inborn Errors of Ketone Body Metabolism In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Nakamura K. et al. 2001. Molecular Genetics and Metabolism. 72: 115-21. PubMed ID: 11161837
  • Sakurai S. et al. 2007. Molecular Genetics and Metabolism. 90: 370-8. PubMed ID: 17236799
  • Zhang G. et al. 2006. Molecular Genetics and Metabolism. 89: 222-6. PubMed ID: 16935016


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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