Propionic Acidemia via the PCCA 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
9453 PCCA 81406 81406,81405 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9453PCCA81406 81405, 81406 $890 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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.

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.

 

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

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).

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.

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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