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Methlymalonyl-CoA Epimerase Deficiency via the MCEE 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
MCEE 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9013MCEE81479 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.

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Methylmalonic acidemia (MMA) without homocystinuria is caused either by errors in the biochemical pathway in which propionyl-CoA is converted to succinyl-CoA, or by defects in the generation of the enzymatic cofactor adenosylcobalamin (AdoCbl) (Dobson et al 2006; Manoli et al. 2016). The vast majority of diagnosed cases of MMA are caused by variants in the MUT gene, followed by the MMAA, MMAB, MMADHC and MCEE genes. Very few patients have been reported to have variants in the MCEE gene, so a cohesive clinical picture has yet to emerge. Symptoms reported in the few MCEE patients thus far include failure to gain weight, gastroesophageal reflux, tachypnea, vomiting and diarrhea. Biochemically, these patients have been found to exhibit mild to moderately increased levels of serum methylmalonic acid and methylcitric acid, as well as severe metabolic acidosis. Plasma total homocysteine levels have been reported to be normal (Bikker et al. 2006; Dobson et al 2006; Gradinger et al. 2007; Manoli et al. 2016). One patient presented with progressive delayed motor development; however, this patient was the child of consanguineous parents and was also diagnosed with sepiapterin deficiency, to which the motor delays were largely attributed (Bikker et al. 2006). MCEE deficiency has also been reported to occur in asymptomatic individuals (Bikker et al. 2006; Dobson et al 2006; Gradinger et al. 2007).

Treatment of the reported patients has included a protein-restricted diet and vitamin B12 supplementation, although too few reports exist to be certain of the efficacy of this regimen (Bikker et al. 2006; Dobson et al 2006).

Genetics

Methlymalonyl-CoA Epimerase Deficiency is thought to be an autosomal recessive disorder, and MCEE is the only gene in which defects occur. To date, fewer than five causative variants have been reported in the MCEE gene (Human Gene Mutation Database; Gradinger et al. 2007). Two of these variants (p.Arg47* and p.Lys60Gln) have been reported in the homozygous state, while the third (p.Arg143Cys) has been reported in the heterozygous state in two patients for whom a second variant was not identified. Of these variants, the p.Arg47* variant appears to be the most common as it has been reported in at least three families (Bikker et al. 2006; Dobson et al 2006; Gradinger et al. 2007).

Methlymalonyl-CoA Epimerase Deficiency is caused by defects in the Methlymalonyl-CoA Epimerase enzyme, which is responsible for the interconversion of the D- and L-methylmalonyl-CoA. The D- and L-methylmalonyl-CoA products are intermediates in the pathway whereby propionyl-CoA is converted to succinyl-CoA (Dobson et al. 2007).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, the sensitivity of this test is difficult to estimate due to the low number of cases reported in the literature. Analytical sensitivity may be high as the only reported causative variants are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the MCEE 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).

This testing also includes coverage for the following intronic variant, as well as ~10 bp of adjacent sequence: c.379-644A>G.

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 serum methylmalonic acid are good candidates for this test, particularly if cellular complementation and/or studies are not able to pinpoint the suspected type of methylmalonic acidemia. Family members of patients known to have MCEE variants are also good candidates, and we will also sequence the MCEE gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
MCEE 608419
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Methylmalonyl-CoA Epimerase Deficiency AR 251120

Related Test

Name
Methylmalonic Acidemia Panel

Citations

  • Bikker H. et al. 2006. Human Mutation. 27: 640-3. PubMed ID: 16752391
  • Dobson C.M. et al. 2006. Molecular Genetics and Metabolism. 88: 327-33. PubMed ID: 16697227
  • Gradinger A.B. et al. 2007. Human Mutation. 28: 1045. PubMed ID: 17823972
  • Human Gene Mutation Database (Bio-base).
  • Manoli I. et al. 2016. Isolated Methylmalonic Acidemia. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301409

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.
  • 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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ORDER OPTIONS

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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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