DNA icon

Methylmalonic Acidemia, cblB type, via the MMAB 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
9697 MMAB 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9697MMAB81405 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.

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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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

Cobalamin (Cbl or vitamin B12) is an important cofactor in homocysteine metabolism and in branched-chain amino acid and odd-chain fatty acid catabolism. A series of inherited inborn errors of cobalamin metabolism have been identified, designated cblA through cblJ. In cblB disorder, the vital cobalamin-dependent cofactor adenosylcobalamin (AdoCbl) cannot be produced. As a result, cblB disorder leads to elevated levels of methylmalonic acid in the blood (Fenton et al. 2014; Manoli et al. 2016).

Methylmalonic acidemia (MMA) is typically a severe disease with onset in infancy. Patients may present with lethargy, vomiting, hepatomegaly, acidosis, hypoglycemia and neutropenia. Many patients die in childhood; those that survive often experience neurological and renal complications. Milder forms of the disease are also known. Today, many cases are detected through routine neonatal screening with tandem mass spectrometry (Fenton et al. 2014; Manoli et al. 2016).

AdoCbl is the cofactor for methylmalonyl-CoA mutase, which is encoded by the MUT gene. In addition to defects in the MUT gene itself, MMA can be caused by defects in genes that encode proteins involved in the generation of AdoCbl. MMA caused by defects in genes other than MUT are generally referred to as cbl types of MMA. Thus far, three distinct genetic variants of cbl type MMA have been identified: cblA, cblB and cblD variant 2 (Martinez et al. 2005; Fenton et al. 2014). CblB type MMA results from deficiency of cob(I)alamin adenosyltransferase, the enzyme that catalyzes the final step in synthesis of adenosylcobalamin (Fenton et al. 2014).

Genetics

Methylmalonic acidemia cblB type is an autosomal recessive disease. The MMAB gene on chromosome 12 encodes the cob(I)alamin adenosyltransferase enzyme, which catalyzes the final step in synthesis of adenosylcobalamin (Fenton et al. 2014). Over 30 causative MMAB sequence variants have been reported to date (Lerner-Ellis et al. 2006; Human Gene Mutation Database). Of these, approximately two-thirds are missense and nonsense, although splicing and regulatory variants, small deletions, insertions and indels have been reported as well (Martinez et al. 2005; Lerner-Ellis et al. 2006; Human Gene Mutation Database). The majority of pathogenic variants reported today seem to cluster in exon 7 of the MMAB gene, and overall three variants seem to be the most commonly reported (p.Arg186Trp, p.Gln234*, and the splice variant c.197-1G>T) (Lerner-Ellis et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

Dobson et al. (2002) found two MMAB pathogenic variants in all six cblB patients studied. Lerner-Ellis et al. (2006) identified two pathogenic variants in the MMAB gene in 34 of 35 cblB patients, and a single pathogenic variant in the last patient. Thus, the clinical sensitivity of this test appears to be near 100%, and analytical sensitivity is also expected to be high as all variants reported to date should be detectable via direct gene sequencing.

To date, no large deletions or duplications have been reported in MMAB (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the MMAB 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 serum methylmalonic acid are good candidates for this test. Family members of patients known to have MMAB variants are also good candidates, and we will also sequence the MMAB gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
MMAB 607568
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Methylmalonic Aciduria Cblb Type AR 251110

Related Test

Name
Methylmalonic Acidemia Panel

Citations

  • Dobson C.M. et al. 2002. Human Molecular Genetics. 11: 3361-9. PubMed ID: 12471062
  • Fenton W.A. et al. 2014. Disorders of Propionate and Methylmalonate Metabolism. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Human Gene Mutation Database (Bio-base).
  • Lerner-Ellis J.P. et al. 2006. Molecular Genetics and Metabolism. 87: 219-25. PubMed ID: 16410054
  • 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
  • Martínez M.A. et al. 2005. Molecular Genetics and Metabolism. 84: 317-25. PubMed ID: 15781192

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×