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Methylmalonic Aciduria and Homocystinuria, cblJ Type, via the ABCD4 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
ABCD4 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11821ABCD481479 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.


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 cblJ. In cblJ deficiency, cobalamin accumulates in lysosomes and cannot be used to synthesize the cofactors adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). As a result, methylmalonyl CoA mutase cannot convert L-methylmalonyl-CoA to succinyl CoA, and methionine synthase cannot convert homocysteine to methionine. Patients have elevated methylmalonic acid and homocysteine concentrations in blood and urine, and some patients with increased propionylcarnitine concentrations are identified through newborn screening (Coelho et al. 2012). Clinical presentations are variable, but include being small for gestational age, feeding difficulties, hypotonia, lethargy, developmental delay, macrocytic anemia, and cardiovascular defects of variable severity (Coelho et al. 2012; Carrillo-Carrasco et al. 1993). Typically, presentation is within the first year and a half of life, but an 8 year-old patient was also diagnosed with a milder phenotype (Kim et al. 2012). Cultured fibroblasts from patients are phenotypically indistinguishable from that of patients with the cblF disorder (LMBRD1 gene) (Coelho et al. 2012).


Mutations in ABCD4 on chromosome 14q24 are responsible for autosomal recessive methylmalonic aciduria and homocystinuria, cblJ type. The ABCD4 gene consists of 19 coding exons and encodes the 606 amino acid ABCD4 protein. ABCD4 contains a transmembrane domain and an ABC transporter or nucleotide-binding domain. This protein localizes to the lysosome and interacts with LMBD1 (deficient protein in cblF type) (Coelho et al. 2012). It is unknown how the LMBD1 and ABCD4 proteins function in transporting cobalamin across the lysosomal membrane. Reported causative mutations include missense, splicing, and a small insertion detectable by sequencing. Two reported mutations occur in the predicted transmembrane domain, whereas two others have been reported in the predicted nucleotide-binding domain (Coelho et al. 2012; Kim et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be almost 100% because all reported mutations thus far are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the ABCD4 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 cblJ deficiency, including infants with a positive newborn screen. Testing is also indicated for family members of patients who have known ABCD4 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ABCD4.


Official Gene Symbol OMIM ID
ABCD4 603214
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Methylmalonic Aciduria and Homocystinuria, cblJ Type AR 614857


  • 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, Kim JC, Miousse IR, Fung S, Moulin M du, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nürnberg P, Thiele H, et al. 2012. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat. Genet. 44: 1152–1155. PubMed ID: 22922874
  • Kim JC, Lee N-C, Hwu PW-L, Chien Y-H, Fahiminiya S, Majewski J, Watkins D, Rosenblatt DS. 2012. Late onset of symptoms in an atypical patient with the cblJ inborn error of vitamin B12 metabolism: diagnosis and novel mutation revealed by exome sequencing. Mol. Genet. Metab. 107: 664–668. PubMed ID: 23141461


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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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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