Succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency via the OXCT1 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11845 | OXCT1 | 81479 | 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.
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.
Clinical Features and Genetics
Clinical Features
Succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises with no apparent symptoms in between (Fukao et al. 2010). Ketoacidotic episodes are characterized by lethargy, poor feeding, tachypnea, vomiting, and coma. Neonatal onset is common, with almost 50% of patients developing their first crisis at the age of two to four days (Fukao et al. 2010); the remaining patients generally experience their first crisis in later infancy (six to 20 months). Although patients do not show clinical symptoms between acute acidotic episodes, serum ketone levels generally remain elevated, even in the postprandial state. Permanent ketosis or ketonuria is a pathognomonic feature of SCOT deficiency (Fukao et al. 2011), but this metabolic disorder cannot be excluded if permanent ketosis/ketonuria is absent (Fukao et al. 2004; Fukao et al. 2010). Treatment for SCOT deficiency may include the administration of intravenous glucose and sodium bicarbonate during acute ketoacidotic episodes. Because urine organic acid analysis and acylcarnitine profiling reveal non-specific findings, enzyme analysis or molecular testing are required for a definitive diagnosis (Fukao et al. 2011).
Genetics
Succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency is an autosomal recessive genetic disorder associated with mutations in the seventeen exon OXCT1 gene located on chromosome 5p13 (Fukao et al. 2000; Kassovska-Bratinova et al. 1996). More than 20 affected children have been reported from various countries, including the United States, Canada, France, Spain, the United Kingdom, the Netherlands, South Africa, and Japan. Succinyl-CoA:3-Oxoacid CoA transferase is a mitochondrial matrix enzyme which catalyzes the reversible transfer of Coenzyme A from succinyl-CoA to acetoacetate (Mitchell et al. 1995). The acetoacetyl-CoA is subsequently converted to acetyl-CoA by acetoacetyl-CoA thiolase and is oxidized in the Krebs cycle. Most cases of SCOT deficiency result from missense mutations in OXCT1, although a small deletion, insertion, and splice site mutation have also been reported as causative for disease (Human Gene Mutation Database; Fukao et al. 2006; Yamada et al. 2007; Fukao et al. 2010). Furthermore, at least one patient harboring an intronic mutation associated with aberrant splicing of two exons has been reported (Hori et al. 2013).
Clinical Sensitivity - Sequencing with CNV PGxome
The clinical sensitivity of this test is currently unknown, as comprehensive assessments of sensitivity using direct sequencing methods have not been cited in the published literature for this rare disorder. Analytical sensitivity should be high because all mutations reported are detectable by sequencing.
No gross deletions or duplications have been reported (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the OXCT1 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 with known or suspected SCOT deficiency. SCOT deficiency should be differentiated from other causes of ketoacidosis in the neonate, including diabetes mellitus, glycogen storage disease type I, propionic acidemia, methylmalonic aciduria, and lactic acidosis (Mitchell et al. 1995). Although SCOT activity can be diagnosed using enzyme assay on cultured fibroblasts, molecular DNA testing may allow diagnosis of this disorder without requiring skin biopsy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in OXCT1.
Candidates for this test are patients with known or suspected SCOT deficiency. SCOT deficiency should be differentiated from other causes of ketoacidosis in the neonate, including diabetes mellitus, glycogen storage disease type I, propionic acidemia, methylmalonic aciduria, and lactic acidosis (Mitchell et al. 1995). Although SCOT activity can be diagnosed using enzyme assay on cultured fibroblasts, molecular DNA testing may allow diagnosis of this disorder without requiring skin biopsy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in OXCT1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| OXCT1 | 601424 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Succinyl-CoA Acetoacetate Transferase Deficiency | 245050 |
Citations
- Fukao T, Ishii T, Amano N, Kursula P, Takayanagi M, Murase K, Sakaguchi N, Kondo N, Hasegawa T. 2010. A neonatal-onset succinyl-CoA:3-ketoacid CoA transferase (SCOT)-deficient patient with T435N and c.658-666dupAACGTGATT p.N220_I222dup mutations in the OXCT1 gene. J. Inherit. Metab. Dis. 33 Suppl 3: S307–313. PubMed ID: 20652411
- Fukao T, Mitchell GA, Song XQ, Nakamura H, Kassovska-Bratinova S, Orii KE, Wraith JE, Besley G, Wanders RJ, Niezen-Koning KE, Berry GT, Palmieri M, et al. 2000. Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations. Genomics 68: 144–151. PubMed ID: 10964512
- Fukao T, Sakurai S, Rolland M-O, Zabot M-T, Schulze A, Yamada K, Kondo N. 2006. A 6-bp deletion at the splice donor site of the first intron resulted in aberrant splicing using a cryptic splice site within exon 1 in a patient with succinyl-CoA: 3-Ketoacid CoA transferase (SCOT) deficiency. Mol. Genet. Metab. 89: 280–282. PubMed ID: 16765626
- Fukao T, Sass JO, Kursula P, Thimm E, Wendel U, Ficicioglu C, Monastiri K, Guffon N, Baric I, Zabot M-T, Kondo N. 2011. Clinical and molecular characterization of five patients with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. Biochim. Biophys. Acta 1812: 619–624. PubMed ID: 21296660
- Fukao T, Shintaku H, Kusubae R, Zhang GX, Nakamura K, Kondo M, Kondo N. 2004. Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA Transferase (SCOT) do not show permanent ketosis. Pediatr. Res. 56: 858–863. PubMed ID: 15496607
- Hori T, Fukao T, Murase K, Sakaguchi N, Harding CO, Kondo N. 2013. Molecular basis of two-exon skipping (exons 12 and 13) by c.1248+5g>a in OXCT1 gene: study on intermediates of OXCT1 transcripts in fibroblasts. Hum. Mutat. 34: 473–480. PubMed ID: 23281106
- Human Gene Mutation Database (Bio-base).
- Kassovska-Bratinova S, Fukao T, Song XQ, Duncan AM, Chen HS, Robert MF, Perez-Cerda C, Ugarte M, Chartrand C, Vobecky S, Kondo N, Mitchell GA. 1996. Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient. Am J Hum Genet 59: 519–528. PubMed ID: 8751852
- Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, Robert MF, Wang SP, Ashmarina L, Lambert M, Lapierre P, Potier E. 1995. Medical aspects of ketone body metabolism. Clin Invest Med 18: 193–216. PubMed ID: 7554586
- Yamada K, Fukao T, Zhang G, Sakurai S, Ruiter JPN, Wanders RJA, Kondo N. 2007. Single-base substitution at the last nucleotide of exon 6 (c.671G>A), resulting in the skipping of exon 6, and exons 6 and 7 in human succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene. Mol. Genet. Metab. 90: 291–297. PubMed ID: 17169596
Ordering/Specimens
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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