• Test code: 06109
  • 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

Invitae Elevated C4 and C5 Panel

Test description

The Invitae Elevated C4 & C5 Panel analyzes 7 genes that are associated with elevations of C4 and C5 acylcarnitines on newborn screening (NBS) or acylcarnitine analysis. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (7 genes)


Alternative tests to consider

The Invitae Fatty Acid Oxidation Defects Panel has been designed to provide a broad genetic analysis of this class of disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional cost.

  • ethylmalonic encephalopathy
  • multiple acyl-coA dehydrogenase deficiency
  • riboflavin transporter deficiency

Elevated C4 and C5 acylcarnitines may be detected during newborn screening due to multiple acyl-coA dehydrogenase (MAD) deficiency or ethylmalonic encephalopathy (EE) or riboflavin transporter deficiency. Disease onset and severity of multiple acyl-CoA dehydrogenase deficiency vary widely. Severely affected patients present in the neonatal period with a “sweaty feet” odor, hypoketotic hypoglycemia, hyperammonemia, acidosis, hypotonia, and hepatomegaly. Some patients may also have congenital anomalies and facial dysmorphism. More mildly affected patients can present as late as adulthood with hypoglycemia, liver dysfunction, and muscle weakness. Infants with ethylmalonic encephalopathy often have acrocyanosis, petechiae, chronic diarrhea, hypotonia, seizures, and abnormal movements. Early treatment may improve the long-term outcomes of these patients. Riboflavin transporter deficiency is typically early onset but adult onset has been reported.

This panel covers all known genetic conditions that can cause elevated C4 and C5 on newborn screening or acylcarnitine analysis.

All causes of elevated C4 and C5 are inherited in an autosomal recessive manner.

The prevalence of elevated C4 and C5 is dependent on laboratory cutoffs and ethnicity. Limited data exist on the rates of false-positive elevations of C4 and C5. The prevalence of confirmed genetic causes of elevated C4 and C5 has been reported as high as 1 in 15,000 in some ethnic groups.

This panel may be appropriate for:

  • infants with elevated C4 and C5 on NBS or confirmatory plasma acylcarnitine analysis
  • patients with elevated C4 and C5 on plasma acylcarnitine analysis with unclear or unavailable 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
ETFA NM_000126.3
ETFB NM_001985.2; NM_001014763.1
ETFDH NM_004453.3
ETHE1 NM_014297.3
SLC52A1 NM_017986.3
SLC52A2 NM_024531.4
SLC52A3 NM_033409.3