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Methylmalonic Aciduria and Homocystinuria, cblD Type, via the MMADHC 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
MMADHC 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8673MMADHC81479 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. 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 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.


Genetic Counselors


  • 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 cblG. The rare cblD disorder shows clinical and biochemical variability, as this disorder may be associated with either isolated or combined deficiency of methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) synthesis (Suormala et al. 2004). In classic cblD disorder, patients have combined homocystinuria and methylmalonic aciduria. However, in cblD variant 1, patients have isolated homocystinuria, and in cblD variant 2, patients have isolated methylmalonic aciduria. Whether patients present with classic cblD, cblD variant 1 or cblD variant 2 seems to depend on the type and location of variants in the MMADHC gene (Carrillo-Carrasco et al. 2013; Watkins and Rosenblatt 2014). Presenting features of cblD deficiency include developmental delay, focal neurologic signs, megaloblastic anemia, marfanoid appearance, venous thrombosis, cerebral atrophy, and hydrocephalus (Miousse et al. 2009; Carrillo-Carrasco et al. 2013; Watkins and Rosenblatt 2014).


Pathogenic variants in MMADHC on chromosome 2q23.2 are responsible for autosomal recessive methylmalonic aciduria and homocystinuria, cblD type. The MMADHC gene consists of eight exons (seven of which encode protein). While the exact function of the gene product remains unknown, it appears to be a cobalamin-binding mitochondrial protein which shows homology to the putative ATPase component of a bacterial ABC transporter (Miousse et al. 2009). To date, fewer than 20 pathogenic variants have been reported in the MMADHC gene. It has been hypothesized that Met62 is capable of acting as a second start codon for reinitiation of translation in patients with an initiation codon or early chain termination variant. These patients would produce a shorter functional protein lacking mitochondrial sequence, but capable of normal methylcobalamin synthesis (Coelho et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

In two studies which examined a total of 10 patients with cblD defect, all individuals were found to have MMADHC pathogenic variants in either a compound heterozygous or homozygous state (Coelho et al. 2008; Miousse et al. 2009).

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

Testing Strategy

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

Candidates for this test are patients with biochemical findings and/or clinical symptoms consistent with cblD deficiency, including infants with a positive newborn screen. Testing is also indicated for family members of patients with known MMADHC mutations. We will also sequence the MMADHC gene to determine carrier status.


Official Gene Symbol OMIM ID
MMADHC 611935
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Methylmalonic Aciduria and Homocystinuria, cblD Type AR 277410

Related Tests

Homocystinuria Panel
Homocystinuria, cblE Type, via the MTRR Gene
Homocystinuria, cblG Type, via the MTR Gene
Methylmalonic Acidemia Panel
Methylmalonic Aciduria and/or Homocystinuria via the CD320 Gene


  • Carrillo-Carrasco N, Adams D, Venditti CP. 2013. Disorders of Intracellular Cobalamin Metabolism. 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: 20301503
  • Coelho D. et al. 2008. The New England Journal of Medicine. 358: 1454-64.  PubMed ID: 18385497
  • Human Gene Mutation Database (Bio-base).
  • Miousse I.R. et al. 2009. The Journal of Pediatrics. 154: 551-6.  PubMed ID: 19058814
  • Suormala T. et al. 2004. The Journal of Biological Chemistry. 279: 42742-9.  PubMed ID: 15292234
  • Watkins and Rosenblatt. 2014. Inherited Disorders of Folate and Cobalamin Transport and Metabolism. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.


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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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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