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  • Test code: 06105
  • 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 Elevated C3 Panel

Test description

The Invitae Elevated C3 Panel analyzes 15 genes that are associated with elevations of C3 (propionylcarnitine) on newborn screening (NBS). Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (15 genes)

ABCD4 BTD CD320 HCFC1 HLCS LMBRD1 MCEE MMAA MMAB MMACHC MMADHC MUT PCCA PCCB TCN2

Add-on ACSF3 Gene (1 gene)

Elevated C3 levels are associated with biallelic pathogenic mutations in ACSF3; however, affected individuals may have a milder presentation and the age of onset is variable, therefore they may not be identified on newborn screening.

ACSF3

Alternative tests to consider

The Invitae Metabolic Disorders Newborn Screening Panel and the Invitae Organic Acidemias Panel have been designed to provide a broad genetic analysis of these classes of disorders. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. They can be ordered at no additional cost.

  • biotinidase deficiency
  • cobalamin A deficiency
  • cobalamin B deficiency
  • cobalamin C deficiency
  • cobalamin D deficiency
  • cobalamin F deficiency
  • cobalamin J deficiency
  • cobalamin X deficiency
  • combined malonic and methylmalonic aciduria due to ACSF3 deficiency
  • holocarboxylase synthetase deficiency
  • methylmalonic acidemia due to mutase deficiency
  • methylmalonyl CoA epimerase deficiency
  • propionyl CoA carboxylase deficiency
  • transcobalamin deficiency
  • transcobalamin receptor deficiency

The elevated C3 (propionylcarnitine) acylcarnitine that is detected during newborn screening may have both genetic and non-genetic causes. Propionic acidemia, methylmalonic acidemia, defects in the metabolism of vitamin B12 (a cofactor for methylmalonyl mutase enzyme), and other inherited disorders that affect propionate metabolism can all cause elevated C3 on newborn screening. Severe vitamin B12 deficiency in the mother—as can be the result of a strict vegan diet, for example—may also cause elevated C3 on newborn screening.

Infants with inherited causes of elevated C3 may present with lethargy, vomiting, seizures, and metabolic acidosis. If untreated, affected infants can progress to coma and death. Since these disorders are treatable, early diagnosis is critical to avoid irreversible damage and to improve long-term outcomes.

This panel covers the vast majority of genetic conditions that can cause elevated C3 on newborn screening or acylcarnitine analysis.

Most genetic causes of elevated C3 are inherited in an autosomal recessive manner. HCFC1 is located on the X chromosome and is also associated with X-linked intellectual disability.

The prevalence of elevated C3 is dependent on laboratory cutoffs and ethnicity. Limited data exist on the rates of false-positive elevations of C3 and on non-genetic causes of elevated C3. The prevalence of confirmed genetic causes of elevated C3 has been reported as high as 1 in 7,300 in some ethnic groups.

This panel may be appropriate for:

  • infants with elevated C3 on NBS or confirmatory plasma acylcarnitine analysis
  • patients with elevated C3 on plasma acylcarnitine analysis with unclear, unavailable, or negative urine organic acid results

For considerations for testing please refer to:

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.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ABCD4 NM_005050.3
ACSF3 NM_174917.4
BTD NM_000060.3
CD320 NM_016579.3
HCFC1 NM_005334.2
HLCS NM_000411.6
LMBRD1 NM_018368.3
MCEE NM_032601.3
MMAA NM_172250.2
MMAB NM_052845.3
MMACHC NM_015506.2
MMADHC NM_015702.2
MUT NM_000255.3
PCCA NM_000282.3
PCCB NM_000532.4
TCN2 NM_000355.3