Invitae Fatty Acid Oxidation Defects Panel


Test description

The Invitae Fatty Acid Oxidation Defects Panel analyzes up to 17 genes that are known to be associated with steps in the fatty acid oxidation pathway. Each fatty acid oxidation defect (FAOD) is due to a specific enzyme or transporter defect in the fatty acid oxidation metabolic pathway. The FAODs are genetically heterogeneous.

This test may be appropriate for anyone in whom a diagnosis of an FAOD is suspected based on clinical symptoms, laboratory findings, or a combination of both. Additionally, many of these genes cause conditions tested on the US Newborn Screening (NBS) panel. The Invitae FAOD Panel may be appropriate for infants who have a presumptive positive biochemical test on NBS, for sick or premature infants with confounding factors complicating NBS interpretation, and even for infants with a normal result on a prior NBS. Many FAODs are episodic, and abnormal metabolites may only be detected during a period of physiologic stress or metabolic crisis.

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Primary panel (16 genes)


Add-on preliminary-evidence gene (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Multiple acyl-CoA dehydrogenase (MCAD) deficiency, short-chain acyl-CoA dehydrogenase (SCAD) deficiency, short-/branched-chain acyl-CoA dehydrogenase (a.k.a. 2-methylbutyryl-CoA dehydrogenase) deficiency, very long chain acyl-CoA dehydrogenase deficiency (VLCAD), carnitine palmitoyltransferase 1 deficiency (CPT1), carnitine palmitoyltransferase 2 deficiency (CPT2), multiple acyl-CoA dehydrogenase deficiency (MADD or glutaric acidemia, type II), long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, mitochondrial trifunctional protein (TFP) deficiency, HMG-CoA Lyase deficiency (3-hydroxy-3-methylglutaryl-CoA lyase deficiency), malonyl-CoA decarboxylase deficiency, primary carnitine deficiency (carnitine transporter deficiency), carnitine-acylcarnitine translocase deficiency (CACT)

Fatty acid oxidation disorders are a broad group of inherited metabolic conditions that result from the inability to adequately metabolize fats for energy. In individuals with an FAOD, fats cannot be broken down, so fatty acids accumulate in tissues, there is a decrease in available ATP, gluconeogenesis cannot occur, and sufficient ketones cannot be generated. This results in an overall lack of energy for tissues and the potential for an acute metabolic crisis.

Fatty acid oxidation disorders have wide clinical heterogeneity, with specific symptoms and laboratory findings corresponding to the location of the metabolic block. In general, symptoms are episodic and correlate with periods of fasting or physiologic stress. During these crises, many patients experience lethargy, fasting hypoketotic hypoglycemia that may progress to metabolic acidosis, liver dysfunction, hypoglycemic seizures, coma, and death. Muscle tissues (both cardiac and skeletal) consume large quantities of fats when glucose is not available;consequently, many individuals with FAOD experience muscular symptoms such as cardiomyopathy, exercise intolerance, and muscle damage due to significant muscle cramping or rhabdomyolysis during a metabolic crisis. Undiagnosed FAODs have also been hypothesized to be the cause of up to 5% of unexpected sudden infant death syndrome (SIDS) cases and other instances of unexplained sudden death. Laboratory findings can include hypoketotic hypoglycemia, elevated creatinine kinase, elevated dicarboxylic acids on urine organic acids, decreased free carnitine, and increased acylcarnitine species corresponding to the metabolic block.

FAODs can present at any time during an individual’s lifespan, and some conditions have infantile through adult presentations. FAODs are often unmasked during a period that combines fasting with physiologic stress, such as illness. These periods increase the metabolic rate and are often accompanied by a diminished appetite; consequently, the body turns to fats for energy. The long-term prognosis for FAOD is generally good once a diagnosis is obtained and interventions such as dietary modifications, medications, and illness protocols are implemented.

All conditions covered by this test are inherited in an autosomal recessive manner. Males and females are equally affected.

Fatty acid oxidation disorders are one of the most common groups of inherited metabolic disorders. Collectively, the overall incidence of all FAODs is 1 in 10,000–14,000 live births.

Incidence of individual FAOD is variable. The incidences of some of the more common conditions are listed below. Adult-onset forms are under-recognized and these numbers are likely low:

  • MCAD: California 1 in 19,000; Northern Germany 1 in 4,900; Japan 1 in 51,000
  • VLCAD: United States 1 in 30,000

This test may be appropriate for:

  • patients who present with lethargy and hypoketotic hypoglycemia, with or without hyperammonemia
  • patients with nonspecific, negative, or unavailable findings on plasma acylcarnitinesor urine organic acid analysis in whom a fatty-acid oxidation defect is still suspected

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, 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
ACADM NM_000016.5
ACADS NM_000017.3
ACADSB NM_001609.3
ACADVL NM_000018.3
CPT1A NM_001876.3
CPT2 NM_000098.2
DECR1 NM_001359.1
ETFA NM_000126.3
ETFB NM_001985.2
ETFDH NM_004453.3
HADH NM_005327.4
HADHA NM_000182.4
HADHB NM_000183.2
HMGCL NM_000191.2
MLYCD NM_012213.2
SLC22A5 NM_003060.3
SLC25A20 NM_000387.5