Pyruvate Dehydrogenase E3-Binding Protein (E3BP) Deficiency via the PDHX 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
8131 PDHX 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8131PDHX81406 81406, 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.

For Reflex to PGxome pricing click here.

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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


Clinical Features and Genetics

Clinical Features

The Pyruvate Dehydrogenase complex (PDHc) is responsible for catalyzing the irreversible, rate-limiting step in the aerobic oxidation of pyruvate to acetyl CoA, thereby effectively linking the cytosolic glycolysis metabolic pathway to the mitochondrial citric acid cycle. The PDHc is a large, multisubunit complex located in the mitochondrial matrix. Multiple enzymatic activities are associated with PDHc and each is carried out by a different subunit within the complex. The different subunits are encoded by several nuclear genes ( PDHA1 , PDHB, DLAT, DLD, PDHX), and activity of the complex is regulated by reversible phosphorylation and dephosphorylation accomplished by PDH kinase (encoded by the PDK1 through PDK4 genes) and PDH phosphatase (encoded by the PDP1 and PDP2 genes) (Robinson 2014).

PDHc deficiency presents with a wide spectrum of disease severity and symptoms, and substantial overlap exists between patients with PDHc deficiency caused by defects in different genes. In general, patients can be classified into three groups based on severity and clinical symptoms. The first group is the most severe, with neonatal onset and death occurring within the first six months of life. These infants typically exhibit low residual PDH activity and severe, chronic lactic acidosis. The second group of patients typically only have mild-to-moderate lactic acidosis, with the acidosis usually only occurring temporarily. Such patients often also present with psychomotor retardation and developmental delay, and approximately 25% die before 3 years of age. Features of Leigh syndrome, such as cystic lesions in the basal ganglia and cerebral atrophy, are common in such patients. The third and most mild form of PDHc deficiency includes patients who present with chronic or episodic ataxia that is often carbohydrate induced, less markedly increased blood lactate levels, varying degrees of intellectual disability, and often no detectable neuropathology, although some may slowly develop lesions in the brain that are typical of Leigh disease. Approximately one-third of PDHc deficient patients show facial dysmorphism similar to that observed in fetal alcohol syndrome patients (shortened palpebral fissures, smooth philtrum, and thin upper lip). Some PDHc deficient patients have shown improvement upon treatment with thiamine, sodium bicarbonate, carnitine, and/or a ketogenic diet (Robinson 2014).


The PHDX gene resides on chromosome 11 (11p13, 11 exons). Defects in this gene are inherited in an autosomal recessive manner. To date, approximately 20 PHDX pathogenic variants have been reported in the literature. The majority of reported variants have been nonsense and splicing, although missense, small deletions and insertions, gross deletions and complex rearrangements have also been reported (Human Gene Mutation Database).

The Pyruvate Dehydrogenase Complex (PDHc) contains three catalytic subunits (E1, E2 and E3), all of which are present in multiple copies in the PDHc. In addition, the E3-Binding Protein (E3BP; previously known as protein X), encoded by the PHDX gene is important for structurally linking the E2 and E3 subunits.

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the PDHX gene are a relatively common cause of Pyruvate Dehydrogenase Complex (PDHc) deficiency. One large study of 82 patients with confirmed PDHc deficiency found that variants in the PDHX gene accounted for ~13% of cases (Imbard et al. 2011), making this the second most common cause of PDHc deficiency. Analytical sensitivity should be relatively high because the great majority of reported variants are detectable by sequencing.

To date, only a small number of gross deletions have been reported in the PDHX gene (Schiff et al. 2006; Imbard et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the PDHX 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals with elevated lactate and pyruvate in blood and cerebral spinal fluid (CSF) and a normal or low lactate to pyruvate ratio and patients with clinical features suggestive of PDHc deficiency are good candidates for this test. Additionally, family members of patients who have known PDHX variants are good candidates. We will also sequence the PDHX gene to determine carrier status.


Official Gene Symbol OMIM ID
PDHX 608769
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Pyruvate Dehydrogenase E3-Binding Protein Deficiency AR 245349

Related Tests

Pyruvate Dehydrogenase E2 Deficiency via the DLAT Gene
Pyruvate Dehydrogenase Phosphatase Deficiency via the PDP1 Gene


  • Human Gene Mutation Database (Bio-base).
  • Imbard A. et al. 2011. Molecular Genetics and Metabolism. 104: 507-16. PubMed ID: 21914562
  • Robinson B.H. 2014. Lactic Acidemia: Disorders of Pyruvate Carboxylase and Pyruvate Dehydrogenase. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Schiff M. et al. 2006. Annals of Neurology. 59: 709-14. PubMed ID: 16566017


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.

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

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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.

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