Very Long Chain Acyl-CoA Dehydrogenase Deficiency via the ACADVL 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
9507 ACADVL 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9507ACADVL81406 81406, 81479 $890 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Very long chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM #201475) is a defect in the breakdown of very long chain (C14-C20) fatty acids within the mitochondria. The severity of VLCADD varies over a wide range and can be divided into three clinical groups:

(1) severe, early-onset, cardiac and multiorgan failure - within the first few months of life, affected individuals present with cardiomyopathy, arrhythmias, pericardial effusion, hepatomegaly, hypotonia, and episodes of hypoketotic hypoglycemia;

(2) hepatic or hypoketotic hypoglycemia - individuals present in early childhood with hepatomegaly and hypoketotic hypoglycemia but without the cardiac issues;

(3) later-onset episodic myopathic form - individuals are diagnosed in adolescence or adult life with muscle weakness and pain, which can be induced by exercise.

VLCADD may be detected through tandem mass spectrometry in routine neonatal screening, though affected individuals with milder phenotypes may not be identified during times of physiologic health. Incidence of VLCADD in the United States is estimated to be 1/30,000.

Genetics

Very long chain acyl-CoA dehydrogenase (VLCAD), encoded by the ACADVL gene, catalyzes the first step in the catabolism of fatty acids with 14-20 carbon atoms. VLCAD deficiency exhibits autosomal recessive inheritance. Hundreds of causative ACADVL variants have been reported to date. Variants are located throughout the gene and are roughly 60% missense and 40% frameshift, splicing, or nonsense. One variant, p.Val283Ala, accounts for 20% of the pathologic alleles among those identified by newborn screening. Variants which completely eliminate enzyme activity usually cause the most severe disease, while missense variants resulting in some residual enzyme activity lead to milder childhood and adult onset forms (Andresen et al. Am J Hum Genet 64:479-494, 1999; Gregersen et al. Hum Mutat 18:169-189, 2001).

Testing Strategy

This test provides full coverage of all coding exons of the ACADVL 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Andresen et al. (Am J Hum Genet 64:479-494, 1999) performed ACADVL gene sequencing on 55 VLCADD patients with demonstrated enzyme deficiency and found two likely causative variants in 47 patients (85%) and one likely causative variant in the remaining 8 patients. Boneh et al. (Mol Genet Metab 88:166-170, 2006) found two causative variants in 6 of 6 patients identified through neonatal screening. Analytical sensitivity should be high because nearly all variants reported to date are expected to be detected by sequence analysis of genomic DNA.

Indications for Test

Infants identified by newborn screening with VLCADD. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ACADVL.

Gene

Official Gene Symbol OMIM ID
ACADVL 609575
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Very Long Chain Acyl-CoA Dehydrogenase Deficiency AR 201475

Citations

  • Andresen, B. S., et.al. (1999). "Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency." Am J Hum Genet 64(2): 479-94. PubMed ID: 9973285
  • Boneh, A., et.al. (2006). "VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis." Mol Genet Metab 88(2): 166-70. PubMed ID: 16488171
  • Gregersen, N., et.al. (2001). "Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship." Hum Mutat 18(3): 169-89. PubMed ID: 11524729

Ordering/Specimens

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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