Propionic Acidemia via the PCCA 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 | |
|---|---|---|---|---|---|
| 9453 | PCCA | 81406 | 81406,81405 | $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
Propionic acidemia (PA; OMIM 606054) is a severe and often lethal defect in the catabolism of certain amino acids (methionine, isoleucine, threonine, valine), odd-numbered chain length fatty acids and cholesterol. PA patients lack substantial activity in the mitochondrial enzyme propionyl-CoA carboxylase. Clinical onset is usually in infancy or early childhood. Clinical features include food intolerance, vomiting, lethargy, failure to thrive, ketoacidosis, hyperammonemia, and neutropenia.
Genetics
Propionic acidemia (PA) is an autosomal recessive condition. Propionyl-CoA carboxylase is comprised of two subunits, alpha and beta, encoded by the PCCA and PCCB genes, respectively. Defects in either gene can cause PA. Roughly 80 different causative variants in PCCA have been reported to date (Desviat et al. Mol Genet Metab 83:28-37, 2004; www.hgmd.org). Causative variants are mostly missense, frameshift, splicing, and nonsense. Some large deletions have been reported as well. Variants are located throughout the length of the gene. Except for founder variants in some isolated populations, no variants are predominant.
Clinical Sensitivity - Sequencing with CNV PGxome
PA patients are about equally split between those with variants in PCCA and those with variants in PCCB. Ugarte et al. (Hum Mut 14:275-282, 1999) reported that about 70% of causative variants were detected in PCCA complementation group patients, but this may be an underestimate due to relatively early, inefficient detection methods. We estimate that at least one likely causative variant will be detected in nearly all patients with low propionyl-CoA carboxylase activity in the PCCA complementation group. Some large deletions (~10% of causative variants), have been reported (www.hgmd.org).
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This test provides full coverage of all coding exons of the PCCA 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.
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
All PA patients are candidates for this test. Many patients will already have had propionyl-CoA carboxylase enzyme assays performed on lymphocyte or fibroblast specimens. While it is possible to biochemically distinguish the two complementation groups in PA patients (see for example Rodriguez-Pombo et al. Am J Hum Genet 63:360-369, 1998), it may be easier to simply perform the DNA tests. In cases where the complementation group is unknown, we recommend sequencing the PCCB gene first. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PCCA.
All PA patients are candidates for this test. Many patients will already have had propionyl-CoA carboxylase enzyme assays performed on lymphocyte or fibroblast specimens. While it is possible to biochemically distinguish the two complementation groups in PA patients (see for example Rodriguez-Pombo et al. Am J Hum Genet 63:360-369, 1998), it may be easier to simply perform the DNA tests. In cases where the complementation group is unknown, we recommend sequencing the PCCB gene first. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PCCA.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| PCCA | 232000 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Propionic Acidemia | AR | 606054 |
Related Tests
| Name |
|---|
| Propionic Acidemia Panel |
| Propionic Acidemia via the PCCB Gene |
Citations
- Desviat, L. R., et.al. (2004). "Propionic acidemia: mutation update and functional and structural effects of the variant alleles." Mol Genet Metab 83(1-2): 28-37. PubMed ID: 15464417
- Human Gene Mutation Database.
- Rodriguez-Pombo, P., et.al. (1998). "Human propionyl-CoA carboxylase beta subunit gene: exon-intron definition and mutation spectrum in Spanish and Latin American propionic acidemia patients." Am J Hum Genet 63(2): 360-9. PubMed ID: 9683601
- Ugarte, M., et.al. (1999). "Overview of mutations in the PCCA and PCCB genes causing propionic acidemia." Hum Mutat 14(4): 275-82. PubMed ID: 10502773
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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ORDER OPTIONS
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2) Select Additional Test Options
No Additional Test Options are available for this test.