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Maple Syrup Urine Disease Type IB via the BCKDHB 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
BCKDHB 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9393BCKDHB81406 81406,81479 $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

Maple syrup urine disease (MSUD; OMIM 248600) is a heterogeneous organic aciduria disorder caused by the impairment of the branched-chain α-keto acid dehydrogenase complex (BCKD). BCKD is a mitochondrial complex, encoded by four nuclear genes (BCKDHA, BCKDHB, DBT, and DLD), which is involved in the metabolism of the branched-chain amino acids leucine, isoleucine, and valine (Morton et al. Pediatrics 109:999-1008, 2002; Nellis et al. Molec Genet Metab 80:189-195, 2003; Chuang et al. J Biol Chem 279:17792-17800, 2004). Defective BCKD complex activity leads to the accumulation of the branch-chain amino acids to toxic levels (Chuang et al. 2004). MSUD, in untreated neonates, is characterized by mental and physical retardation, maple syrup odor in cerumen and urine, poor feeding, ketonuria, irritability, lethargy, intermittent apnea, opisthotonus, stereotyped movements such as “fencing” and “bicycling,” coma, and respiratory failure. Biochemically, MSUD is characterized by elevated plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) and allo-isoleucine, as well as a generalized disturbance of plasma amino acid concentration ratios (Schadewaldt et al. Clin Chem 45:1734-1740, 1999; Morton et al. 2002; Nellis et al. 2003; Chuang et al. 2004).


MSUD is an autosomal recessive genetically heterogeneous disorder caused by variants in one of the four BCKD complex encoded genes (BCKDHA, BCKDHB, DBT, and DLD). MSUD Type IB is caused by variants in the BCKDHB gene, which encodes the 2-oxoisovalerate dehydrogenase subunit beta of the of the BCKD complex (Nobukuni et al. J Clin Invest 87:1862-1866, 1991; Mitsubuchi et al. J Biol Chem 266:14686-14691, 1991; Chuang et al. Am J Hum Genet 58: 1373-1377, 1996). A mix of missense, nonsense, splicing, small insertion and deletion variants as well as gross deletion variants within the BCKDHB gene have been reported (Nobukuni et al. 1991; Henneke et al. Hum Mutat 22:417-422, 2003; Chuang et al. 2004; Rodriguez et al. Hum Mutat 27:715-727, 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

It has been reported that variants in the BCKDHB gene are responsible for approximately 38% of the MSUD cases, while variants in the BCKDHA and the DBT genes are responsible for approximately 33% and 19% of MSUD cases, respectively (Nellis and Danner. Am J Hum Genet 68:232-237, 2001).

Testing Strategy

This test provides full coverage of all coding exons of the BCDKHB 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 symptoms consistent with MSUD and family members of patients who have known BCKDHB variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BCKDHB.


Official Gene Symbol OMIM ID
BCKDHB 248611
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Maple Syrup Urine Disease AR 248600

Related Tests

Maple Syrup Urine Disease Panel
Maple Syrup Urine Disease Type IA via the BCKDHA Gene


  • Chuang, J. L., et.al. (1996). "Maple syrup urine disease: the E1beta gene of human branched-chain alpha-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3' UTR in one of the two E1beta mRNAs arises from intronic sequences." Am J Hum Genet 58(6): 1373-7. PubMed ID: 8651316
  • Chuang, J. L., et.al. (2004). "Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype." J Biol Chem 279(17): 17792-800. PubMed ID: 14742428
  • Henneke, M., et.al. (2003). "Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease." Hum Mutat 22(5): 417 - 422. PubMed ID: 14517957
  • Mitsubuchi, H., et.al. (1991). "Structural organization and chromosomal localization of the gene for the E1 beta subunit of human branched chain alpha-keto acid dehydrogenase." J Biol Chem 266(22): 14686-91. PubMed ID: 1860867
  • Morton, D. H., et.al. (2002). "Diagnosis and treatment of maple syrup disease: a study of 36 patients." Pediatrics 109(6): 999-1008. PubMed ID: 12042535
  • Nellis, M. M., Danner, D. J. (2001). "Gene preference in maple syrup urine disease." Am J Hum Genet 68(1): 232-7. PubMed ID: 11112664
  • Nellis, M. M., et.al. (2003). "Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression." Mol Genet Metab 80(1-2): 189-95. PubMed ID: 14567968
  • Nobukuni, Y., et.al. (1991). "Maple syrup urine disease. Complete defect of the E1 beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease." J Clin Invest 87(5): 1862-6. PubMed ID: 2022752
  • Rodriguez-Pombo, P., et.al. (2006). "Mutational spectrum of maple syrup urine disease in Spain." Hum Mutat 27(7): 715-727. PubMed ID: 16786533
  • Schadewaldt, P., et.al. (1999). "Significance of L-alloisoleucine in plasma for diagnosis of maple syrup urine disease." Clin Chem 45(10): 1734-40. PubMed ID: 10508118


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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