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Isovaleric Acidemia via the IVD 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
IVD 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9667IVD81406 81406,81479 $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

Isovaleric acidemia (OMIM 243500) is a metabolic defect in the catabolism of the branched-chain amino acid leucine. Isovaleric acidemia patients have deficiency in the activity of the mitochondrial enzyme isovaleryl-CoA dehydrogenase (Rhead and Tanaka. Proc Nat Acad Sci USA 77:580-583, 1980). This deficiency leads to abnormally high concentrations of isovaleric acid in cells, blood, and urine. Isovaleric acid is toxic to the CNS. Clinically, isovaleric acidemia exhibits wide variation in severity. The acute, neonatal form presents with massive metabolic acidosis in the first days of life. Poor feeding, vomiting, and seizures follow and coma and death are often the outcomes. At the other end of the spectrum, the chronic form of isovaleric acidemia exhibit periodic crisis of severe ketoacidosis, but otherwise asymptomatic intervening periods. Intermediate forms may have a childhood onset and are characterized by varying degrees of developmental delay and recurrent episodes of vomiting and lethargy. Patients often have the distinctive “sweaty feet” odor of isovaleric acid during acute illness. Patients can sometimes suffer stroke, and cerebellar hemorrhage has been described in some organic acidemias, including isovaleric acidemia (Testai and Gorelick. Arch Neurol 67:148-153, 2010). Isovaleric acidemia can mimic propionic acidemia and methylmalonic acidemia by producing hyperglycinemia, leukopenia, and episodic ketoacidosis (Ando et al. Pediat Res 5:827-832, 1971). Early diagnosis appears to be highly beneficial for patients.


Isovaleric acidemia is an autosomal recessive disorder. Nearly 40 different IVD causative variants have been reported. The majority of these variants result in amino acid substitutions. Ensenauer et al. (Am J Hum Genet 75:1136- 42, 2004) reported that one common variant, c.941C>T (p.Ala314Val; also referred to in the literature as c.932C>T [p.Ala311Val or p.Ala282Val]), comprises ~50% of variants in patients detected through newborn screening. Importantly, these authors found the same abnormal genotype among siblings who had biochemical evidence of isovaleric acidemia but no clinical symptoms of the disease.

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity should be high because all reported variants are detectable by sequencing. Clinical sensitivity should also be high. For example, Ensenauer et al.  reported the detection by DNA sequencing of two likely causative IVD variants in 18 out of 19 patients identified through newborn screening. Only one causative variant was found in the 19th child (Ensenauer et al. Am J Hum Genet 75:1136-1142, 2004).

Testing Strategy

This test provides full coverage of all coding exons of the IVD 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 elevated 3-OH isovaleric acid and conjugated isovaleryl glycine in urine. Evaluation of serum amino acids is not considered diagnostic. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in IVD.


Official Gene Symbol OMIM ID
IVD 607036
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Isovaleryl-CoA Dehydrogenase Deficiency AR 243500


  • Ando, T., et.al. (1971). "Propionic acidemia in patients with ketotic hyperglycinemia." J Pediatr 78(5): 827-32. PubMed ID: 5581587
  • Ensenauer, R., et.al. (2004). "A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening." Am J Hum Genet 75(6): 1136-42. PubMed ID: 15486829
  • Rhead, W. J., Tanaka, K. (1980). "Demonstration of a specific mitochondrial isovaleryl-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia." Proc Natl Acad Sci U S A 77(1): 580-3. PubMed ID: 6928646
  • Testai, F. D., Gorelick, P. B. (2010). "Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders." Arch Neurol 67(2): 148-53. PubMed ID: 20142522


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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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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