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Glutaric Acidemia Type II via the ETFA Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
ETFA 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9345ETFA81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Glutaric acidemia (GA) type II, also known as multiple acyl-CoA dehydrogenase deficiency (MADD), is an inherited disorder of fatty acid and amino acid oxidation. GA type II is caused by defects in one of three genes (ETFA, ETFB or ETFDH). Clinical and biochemical features are not typically useful in distinguishing which gene is affected in GA type II patients. Three sub-categories of GA type II are recognized, each of which is based on severity and presentation of clinical symptoms (Frerman and Goodman 2014).

Patients in the first group present within the first 48 hours of life with severe hypoketotic hypoglycemia, hypotonia, metabolic acidosis, possibly hepatomegaly and a “sweaty feet” odor similar to that observed in isovaleric acidemia patients, and multiple congenital anomalies, such as dysplastic kidneys, facial dysmorphism, rocker bottom feet, abdominal wall defects and abnormal external genitalia. Such patients typically die within the first week of life (Olsen et al. 2003; Schiff et al. 2006; Frerman and Goodman 2014; Xi et al. 2014).

Patients in the second group present similarly to those in the first group, but without congenital anomalies. If these patients survive beyond the first week of life, they typically succumb within the first few months, often due to cardiomyopathy (Olsen et al. 2003; Schiff et al. 2006; Frerman and Goodman 2014; Xi et al. 2014).

The patients in the third group have a more mild form of GA type II, with onset anywhere from infancy to adulthood. Clinical presentation also varies widely in this group, and may include vomiting, hypoglycemia, metabolic acidosis, hepatomegaly, progressive lipid storage proximal myopathy and exercise intolerance. Symptoms in the third group often present in an episodic manner, making biochemical analysis challenging as abnormalities may be detectable only during periods of metabolic crisis (Olsen et al. 2003; Schiff et al. 2006; Frerman and Goodman 2014; Xi et al. 2014).

In all GA type II patients, generalized aminoacidemia and aminoaciduria, hyperammonemia and metabolic acidosis may be observed. Increased levels of sarcosine in both the serum and urine are common in those with mild, later onset GA type II. Biochemically, GA type II can be distinguished from GA type I based on the presence of 2-hydroxyglutaric acid (3-hydroxyglutaric acid is present in GA type I patients) (Frerman and Goodman 2014).

To date, no effective treatments are available for patients with the severe, infantile onset forms of GA type II. Some patients with the mild, later onset form have been shown to respond well to riboflavin, glycine and L-carnitine supplementation, as well as to dietary restriction of fat and protein (Olsen et al. 2007; Wen et al. 2013; Frerman and Goodman 2014). The majority of patients reported with the late-onset, riboflavin responsive form of GA type II have had defects in the ETFDH gene (Olsen et al. 2007; Wen et al. 2010; Cornelius et al. 2012; Wen et al. 2013).


Glutaric acidemia type II is an autosomal recessive disorder caused by pathogenic variants in the ETFA, ETFB or ETFDH genes. To date, over 25 causative variants have been reported in the ETFA gene (Human Gene Mutation Database). The majority of reported pathogenic variants are missense, although nonsense variants, small deletions, insertions and duplications have all been reported. The variants are spread throughout the gene, and the most commonly reported variant is Thr266Met (Schiff et al. 2006; Frerman and Goodman 2014).

The ETFA gene is located on chromosome 15 and contains 12 exons. ETFA encodes the a-subunit of the electron transfer flavoprotein (ETF). The ETF protein is found in the mitochondrial matrix as a heterodimer, comprised of one subunit each of α- and β-monomers. ETF accepts electrons from at least 12 other flavoprotein dehydrogenases, then transfers them to the mitochondrial respiratory chain via the electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO), encoded by the ETFDH gene. Clinical symptoms observed in ETFA deficient patients are due to a disruption of electron transfer to the respiratory chain (Cornelius et al. 2012; Frerman and Goodman 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Glutaric acidemia II patients are split between those with causative variants in the ETFA, ETFB and ETFDH genes, and it is difficult to estimate the fraction with variants in each gene. However, to date all reported causative variants in the ETFA gene are detectable via direct sequencing, and in studies with somewhat larger numbers of patients with ETFA variants the majority had two variants identified (for example, 23 alleles found in 13 patients, for an overall analytical sensitivity of ~88%; Schiff et al. 2006).

To date, no large deletions or duplications have been described in the ETFA gene, although most studies of glutaric acidemia type II patients that included ETFA analysis have not been reported to have included deletion and duplication testing.

Testing Strategy

This test provides full coverage of all coding exons of the ETFA gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with a positive newborn screening result for glutaric acidemia type II are good candidates for this test, as are individuals that exhibit biochemical and clinical symptoms of GA type II. Family members of patients known to have ETFA variants are also good candidates, and we will also sequence the ETFA gene to determine carrier status.


Official Gene Symbol OMIM ID
ETFA 608053
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Glutaric Aciduria, Type 2 AR 231680

Related Tests

Coenzyme Q10 Ubiquinone Deficiency Panel
Glutaric Acidemia Type II Panel
Glutaric Acidemia Type II via the ETFB Gene


  • Cornelius N. et al. 2012. Human Molecular Genetics. 21: 3435-48. PubMed ID: 22611163
  • Frerman F.E. and Goodman S.I. 2014. Defects of Electron Transfer Flavoprotein and Electron Transfer Flavoprotein-Ubiquinone Oxidoreductase: Glutaric Acidemia Type II. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Human Gene Mutation Database (HGMD).
  • Olsen R.K. et al. 2003. Human Mutation. 22: 12-23. PubMed ID: 12815589
  • Olsen R.K. et al. 2007. Brain. 130: 2045-54. PubMed ID: 17584774
  • Schiff M. et al. 2006. Molecular Genetics and Metabolism. 88: 153-8. PubMed ID: 16510302
  • Wen B. et al. 2010. Journal of Neurology, Neurosurgery, and Psychiatry. 81: 231-6. PubMed ID: 19758981
  • Wen B. et al. 2013. Molecular Genetics and Metabolism. 109: 154-60. PubMed ID: 23628458
  • Xi J. et al. 2014. Journal of Inherited Metabolic Disease. 37: 399-404. PubMed ID: 24357026


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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