The Invitae Elevated C0/(C16+C18) Test analyzes the CPT1A gene, which is associated with elevations of the C0/(C16+C18) acylcarnitine ratio on newborn screening (NBS) or plasma acylcarnitine analysis. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions.
The Invitae Fatty Acid Oxidation Defects Panel has been designed to provide a broad genetic analysis of fatty acid oxidation defects. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional cost.
Carnitine palmitoyltransferase I (CPT1) deficiency
Carnitine palmitoyltransferase I (CPT1) deficiency can lead to elevated C0/(C16+C18) acylcarnitine ratio that may be detected during newborn screening or acylcarnitine analysis. Patients with this disorder typically present in early childhood with episodes of hypoketotic hypoglycemia and hepatic encephalopathy during periods of intercurrent illness or increased fasting. Free fatty acids and liver transaminases may be elevated during attacks, but they may also be elevated during asymptomatic periods. Cardiac- and skeletal-muscle involvement is uncommon. Some patients may develop hepatomegaly and renal tubular acidosis. Some cases of sudden infant death syndrome (SIDS) have been attributed to CPT1 deficiency. Milder forms of CPT1 deficiency have been reported.
A low-fat diet with medium-chain triglyceride (MCT) supplementation and an avoidance of fasting have been used to treat patients with CPT1 deficiency. Early diagnosis and detection may improve the long-term outcome of these patients by reducing or preventing attacks of hepatic encephalopathy.
Pregnant females (obligate carriers) of fetuses affected with CPT1 deficiency are at increased risk of developing acute fatty liver of pregnancy. Symptomatic mothers may develop hypoglycemia, elevated LFTs, and hyperammonemia, leading to impaired liver function and coagulopathy.
For patients with biochemical features consistent with CPT1 deficiency (elevated C0/[C16+C18] on acylcarnitines or elevated free-to-total plasma carnitine ratio), approximately >99% will have two pathogenic variants in CPT1A.
CPT1 deficiency is inherited in an autosomal recessive manner.
The prevalence of elevated C0/(C16+C18) acylcarnitine ratio is dependent on laboratory cutoffs and ethnicity. The overall prevalence of CPT1 deficiency is very rare. The frequency of a mild form of CPT1 is high among the Canadian and Greenland Inuit, BC First Nations, and Alaska Natives populations; it has been estimated in at least 1 in 400 individuals.
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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|