Medium Chain Acyl-CoA Dehydrogenase Deficiency via the ACADM 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
9505 ACADM 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9505ACADM81479 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

Medium chain acyl-CoA dehydrogenase deficiency (MCADD, OMIM #201450) is a defect in the catabolism of fatty acids within the mitochondria. Currently, the majority of new patients are identified through tandem mass spectrometry in neonatal screening. Patients who are identified clinically typically present within the first two years of life with an episode of lethargy and vomiting accompanied by hypoketotic hypoglycemia, which is commonly triggered by a viral infection. Some patients also have hepatomegaly and acute liver disease. These symptoms may progress to seizures, coma, and death. If MCADD is diagnosed early, most mortality and morbidity can be prevented through relatively simple measures, such as frequent feedings to avoid any extended periods of fasting (Wilcken et al. Lancet 369:37-42, 2007). MCADD is one of the most common monogenic metabolic disorders with an incidence of about 1 in 15,000 newborns in the United States. A significant fraction of sudden infant death victims have MCADD (Boles et al. J Pediatr 132:924-933, 1998).

Genetics

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disease. Medium chain acyl-CoA dehydrogenase, encoded by the ACADM gene, catalyzes the first step in the breakdown of fatty acids with 4-12 carbon atoms. For patients with Northern European ancestry, one missense variant in exon 11 (c.985A>G, p.Lys304Glu) is predominant, comprising up to about 76% of alleles in individuals with MCAD deficiency. This variant tends to cause particularly severe disease. At least 90 other causative missense, frameshift, splicing, and nonsense variants as well as gross deletions have been described throughout the length of the gene; most are private variants. Individuals who are compound heterozygous for the p.Lys304Glu variant, or homozygous for other variants in the ACADM gene, tend to have less severe disease. It appears that diagnosis by tandem mass spectrometry is more sensitive than diagnosis by other clinical features and may identify subclinical cases (Andresen et al. Am J Hum Genet 68:1408-18, 2001; Maier et al. Hum Mut 25:443-52, 2005; Matern and Rinaldo, GeneReviews, 2005; and Waddell et al. Mol Genet Metab 87:32-9, 2006).

Testing Strategy

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

Sensitivity of this test appears to be high. Approximately 50% of patients are homozygous for the p.Lys304Glu variant, and 40% of affected individuals are heterozygous for this variant (Matern and Rinaldo, GeneReviews, 2012).

Indications for Test

Newborns suspected to have MCADD based on clinical features or by tandem mass spectroscopy findings. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ACADM.

Gene

Official Gene Symbol OMIM ID
ACADM 607008
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Andresen BS, Dobrowolski SF, O'Reilly L, Muenzer J, McCandless SE, Frazier DM, Udvari S, Bross P, Knudsen I, Banas R, Chace DH, Engel P, Naylor EW, Gregersen N. 2001. Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet 68: 1408-1418. PubMed ID: 11349232
  • Boles, R. G., et.al. (1998). "Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life." J Pediatr 132(6): 924-33. PubMed ID: 9627580
  • Dietrich Matern, Piero Rinaldo (2005). "Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency." PubMed ID: 20301597
  • Maier, E. M., et.al. (2005). "Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency." Hum Mutat 25(5): 443-52. PubMed ID: 15832312
  • Waddell, L., et.al. (2006). "Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations." Mol Genet Metab 87(1): 32-9. PubMed ID: 16291504
  • Wilcken, B., et.al. (2007). "Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study." Lancet 369(9555): 37-42. PubMed ID: 17208640

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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