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.
ETFA ETFB ETFDH ETHE1 SLC52A1 SLC52A2 SLC52A3
ETFA ETFB ETFDH ETHE1 SLC52A1 SLC52A2 SLC52A3
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.
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:
For considerations for testing please refer to:
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|