Short Chain Acyl-CoA Dehydrogenase Deficiency via the ACADS 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
8461 ACADS 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8461ACADS81405 81405, 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

Short chain acyl-CoA dehydrogenase deficiency (SCADD, OMIM #201470) is a defect in the breakdown of fatty acids within the mitochondria that causes accumulation of butyrylcarnitine and ethylmalonic acid in the blood and urine. Currently, the majority of new patients are identified through tandem mass spectrometry in neonatal screening, and they remain asymptomatic. However, older patients identified through clinical symptoms commonly have chiefly neuromuscular symptoms including hypotonia, developmental delay, and seizures. Other reported symptoms include speech delay, feeding difficulty, vomiting, hypoglycemia, and lethargy. Further studies are needed to clarify the relationship between variants in the SCAD gene and disease, and the long term consequences of SCADD (van Maldegem et al. JAMA 296:943-952, 2006; Jethva et al. Mol Genet Metab 95:195-200, 2008; Pedersen et al. Hum Genet 124:43-56, 2008).

Genetics

Short chain acyl-CoA dehydrogenase (SCAD), encoded by the ACADS gene (OMIM #606886), catalyzes one of the steps in the breakdown of fatty acids with short carbon chains, particularly butyryl-CoA. SCAD deficiency is an autosomal recessive inborn error of metabolism. Unlike most other genetic diseases causing fatty acid oxidation defects, the vast majority of variants reported to date in ACADS have been missense variants. It may well be that complete absence of short chain acyl-CoA dehydrogenase activity is lethal. Two common sequence variants in ACADS, c.511C>T (p.Arg171Trp, rs1800556; frequency of T allele ~3%) and c.625G>A (p.Gly209Ser, rs17848088; frequency of A allele ~20%), impair folding and stability. These variants are thought to modify or even cause the disorder in combination with adverse cellular conditions, especially when homozygous for the rare alleles. Genotype-phenotype correlations have not been identified at this time, though genotype correlates well with biochemical profiles (Corydon et al. Pediatr Res 49:18- 23, 2001; van Maldegem et al. 2006; Waisbren et al. Mol Genet Metab 95:39-45, 2008).

Testing Strategy

This test provides full coverage of all coding exons of the ACADS 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

Incidence of SCADD has been estimated at 1/33,000 births, using a cut-off for butyrylcarnitine of 1.9µmol/L (Waisbren et al. Mol Genet Metab 95:39-45, 2008). Analytical sensitivity should be high because 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 SCADD. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ACADS.

Gene

Official Gene Symbol OMIM ID
ACADS 606885
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deficiency Of Butyryl-CoA Dehydrogenase AR 201470

Citations

  • Corydon, M. J., et.al. (2001). "Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency." Pediatr Res 49(1): 18-23. PubMed ID: 11134486
  • Jethva, R., et.al. (2008). "Short-chain acyl-coenzyme A dehydrogenase deficiency." Mol Genet Metab 95(4): 195-200. PubMed ID: 18977676
  • Pedersen, C. B., et.al. (2008). "The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level." Hum Genet 124(1): 43-56. PubMed ID: 18523805
  • van Maldegem, B. T., et.al. (2006). "Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency." Jama 296(8): 943-52. PubMed ID: 16926354
  • Waisbren, S. E., et.al. (2008). "Short-chain acyl-CoA dehydrogenase (SCAD) deficiency: an examination of the medical and neurodevelopmental characteristics of 14 cases identified through newborn screening or clinical symptoms." Mol Genet Metab 95(1-2): 39-45. PubMed ID: 18676165

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

loading Loading... ×

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.

Total Price: $
×
Copy Text to Clipboard
×