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  • Test code: 06219
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Pyruvate Carboxylase Deficiency Test

Test description

The Invitae Pyruvate Carboxylase Deficiency Test analyzes the PC gene that is associated with pyruvate carboxylase deficiency. The PC gene encodes pyruvate carboxylase, a mitochondrial enzyme involved in many metabolic pathways. Pyruvate carboxylase deficiency constitutes a combined deficit in the tricarboxylic acid (TCA) cycle and gluconeogenesis. Clinical manifestations are primarily lactic acidosis and severe neurological dysfunction although there is a wide spectrum of clinical phenotypes varying from life-threatening neonatal lactic acidosis to relatively normal adult life. This test is useful for the diagnosis of patients whose clinical symptoms or biochemical findings indicate pyruvate carboxylase deficiency. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide risk assessment and carrier status for at-risk relatives.

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Primary panel (1 gene)
  • pyruvate carboxylase deficiency
    • pyruvate carboxylase deficiency type A, an infantile form
    • pyruvate carboxylase deficiency type B, a neonatal form
    • pyruvate carboxylase deficiency type C, a mild form

The PC gene encodes pyruvate carboxylase, a mitochondrial enzyme involved in many metabolic pathways, including gluconeogenesis, lipogenesis, synthesis of neurotransmitters, and replenishment of TCA cycle intermediates. Pyruvate carboxylase deficiency constitutes a combined deficit in the tricarboxylic acid (TCA) cycle and gluconeogenesis.

PC deficiency is an inborn error of metabolism with variable severity and ages of onset. Some patients present with psychomotor retardation in the infantile period, an increase of plasma lactate with normal lactate to pyruvate ratio and survival up to 5 years (type A). Other patients present with severe neonatal lactic acidosis, neurological symptoms, elevated lactate-to-pyruvate ratio, hyperammonemia, hyperlysinemia, and hypercitrullinemia, with survival of less than three months (type B). In both forms, hepatomegaly, seizures and failure to thrive may occur. In addition, a few patients with a mild form of PC deficiency, characterized by mild lactic acidemia with normal psychomotor development (type C) have been reported.

Biallelic pathogenic mutations are detected in > 95% of patients diagnosed with pyruvate carboxylase deficiency.

Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner.

The estimated incidence of pyruvate carboxylase deficiency is 1: 250,000 births worldwide. This disorder is much more common in some Algonkian Indian tribes in eastern Canada.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
PC* NM_000920.3

PC: Analysis includes the intronic variant NM_000920.3:c.1369-29A>G.