The Invitae Elevated C4 & C5 Panel analyzes four 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
ETFA ETFB ETFDH ETHE1
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.
Multiple acyl-coA dehydrogenase deficiency, ethylmalonic encephalopathy
Elevated C4 and C5 acylcarnitines may be detected during newborn screening due to multiple acyl-coA dehydrogenase (MAD) deficiency or ethylmalonic encephalopathy (EE). 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.
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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
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|