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Branched-Chain Ketoacid Dehydrogenase Kinase Deficiency via the BCKDK Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4101 BCKDK 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4101BCKDK81479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

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


  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurodevelopmental disorder characterized by intellectual disability and epileptic activity. Patients present with psychomotor delay within the first two years of life, most often noticed as delayed milestones such as walking and talking (Novarino et al. 2012; García-Cazorla et al. 2014). Microcephaly, without any abnormalities detected by MRI, is common in BCKDKD. Patients may experience febrile or afebrile seizures, but even in absence of seizures epileptic activity is detected via EEG. BCKDKD patients have moderate to severe intellectual disability and have noticeable language and social deficits resembling autism spectrum disorders. Reduced plasma levels of branched-chain amino acids (BCAAs) have been seen in all reported BCKDKD patients.


BCKDKD is inherited in an autosomal recessive manner and is caused by variants in the BCKDK gene. Missense, nonsense, splice site, and frameshift variants in BCKDK have been reported (Novarino et al. 2012; García-Cazorla et al. 2014).

BCKDK encodes the kinase BDK. Branched-chain amino acids (BCAAs) are required for a variety of biological processes. BCAAs are broken down by the BCKDH complex. BCKDH activity is regulated by the kinase BDK. When BCKDH is phosphorylated by BDK it is inactive and cannot break down BCAAs. When BCKDK is mutated BDK function is lost and BCKDH remains unphosphorylated and completely active (Harris et al. 2005). High BCKDH activity leads to reduced serum levels of BCAAs. Imbalance of these amino acids is believed to underlie the neurological phenotypes associated with BCKDKD. BDK knockout mice show reduced levels of BCAAs in the blood, brain, heart, muscle, and kidney. In addition, BDK-/- mice show impaired growth, have an abnormal gait, and are prone to seizures (Joshi et al. 2006). There is evidence in mice and humans that supplementation with diets high in BCAAs can help treat some of the symptoms of BCKDKD (Joshi et al. 2006; Novarino et al. 2012; García-Cazorla et al. 2014).

Clinical Sensitivity - Sequencing with CNV PG-Select

The frequency of BCKDK mutations in BCKDKD or epilepsy cases is currently unknown, but all reported BCKDK mutations would be detected via this sequencing method (Novarino et al. 2012; García-Cazorla et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the BCKDK gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

BCKDK sequencing is recommended for patients with intellectual disability and seizures who have reduced plasma BCAA levels. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BCKDK.


Official Gene Symbol OMIM ID
BCKDK 614901
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • García-Cazorla A, Oyarzabal A, Fort J, Robles C, Castejón E, Ruiz-Sala P, Bodoy S, Merinero B, Lopez-Sala A, Dopazo J, Nunes V, Ugarte M, et al. 2014. Two Novel Mutations in the BCKDK (Branched-Chain Keto-Acid Dehydrogenase Kinase) Gene Are Responsible for a Neurobehavioral Deficit in Two Pediatric Unrelated Patients. Human Mutation 35: 470–477. PubMed ID: 24449431
  • Harris RA, Joshi M, Jeoung NH, Obayashi M. 2005. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. The Journal of nutrition 135: 1527S–1530S. PubMed ID: 15930464
  • Joshi MA, Jeoung NH, Obayashi M, Hattab EM, Brocken EG, Liechty EA, Kubek MJ, Vattem KM, Wek RC, Harris RA. 2006. Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice. Biochemical Journal 400: 153. PubMed ID: 16875466
  • Novarino G, El-Fishawy P, Kayserili H, Meguid NA, Scott EM, Schroth J, Silhavy JL, Kara M, Khalil RO, Ben-Omran T, Ercan-Sencicek AG, Hashish AF, et al. 2012. Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy. Science 338: 394–397. PubMed ID: 22956686


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

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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: $
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