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Phosphoglycerate Kinase Deficiency via the PGK1 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
11579 PGK1 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11579PGK181479 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Phosphoglycerate Kinase (PGK) deficiency is a metabolic disorder with patients presenting with variable nonspherocytic hemolytic anemia, myopathy, and central nervous system (CNS) disability. Age at onset is variable with patients primarily presenting with either nonspherocytic hemolytic anemia (60% of cases) or myopathy (30% of cases). Only a few cases have been reported with patients exhibiting both anemia and myopathy (10% of cases) (Beutler 2007; DiMauro et al. 1981). Anemia can result in pallor, jaundice, fatigue, and shortness of breath. Myopathy is characterized by exercise intolerance, myoglobinuria, cramps, myalgia, and muscle weakness. CNS symptoms occur in about half of PGK cases, irrespective of anemia or myopathy, and include seizures, intellectual disability, epilepsy, hemiplegic migraines, and ataxia. Genetic testing is helpful in the differential diagnosis of PGK deficiency from other forms of nonspherocytic hemolytic anemia and myopathic glycogen storage disorders. Iron supplements, blood transfusions as needed, and avoidance of strenuous exercise are standard treatment. In some severe cases, bone marrow transplantation and splenectomy have been shown to be beneficial (Beutler 2007).

Genetics

PGK deficiency is inherited in an X-linked recessive manner through pathogenic variants in the PGK1 gene. Heterozygous females have been reported to have milder forms of hemolytic anemia, but are primarily asymptomatic. The majority of causative variants to date are missense variants resulting in reduced catalytic activity or protein stability. Complete loss of PGK function is thought to be incapable with life. Splice site variants and in-frame insertions/deletions resulting in functional but impaired PGK protein have also been described (Beutler 2007; Fermo et al. 2012; Noel et al. 2005). There is no clear genotype/phenotype correlation, but missense variants in the c-terminal domain near the substrate binding pocket are common for patients with myopathy. The PGK1 gene encodes the phosphoglycerate kinase which facilitates ATP generation during glycolysis. Anemia is typically seen as red blood cells rely on glycolysis for energy production and are unable to synthesize PGK lost due to protein instability (Chiarelli et al. 2012; Pey et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Only about 30 families have been reported to date with PGK deficiency. Analytical sensitivity should be high as all reported pathogenic variants in the PGK1 gene are detectable by sequencing. Clinical sensitivity cannot be estimated because only a small number of cases have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the PGK1 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 testing include patients presenting with variable nonspherocytic anemia, myopathy, and CNS impairment. Ideal candidates have biochemical data showing impaired PGK1 activity or antigen levels in erythrocyte or muscle biopsy tissue. In some cases, creatine kinase can be elevated (Beutler 2007).

Gene

Official Gene Symbol OMIM ID
PGK1 311800
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Phosphoglycerate Kinase 1 Deficiency XL 300653

Citations

  • Beutler E. 2007. British journal of haematology. 136: 3-11. PubMed ID: 17222195
  • Chiarelli LR. et al. 2012. PloS one. 7: e32065. PubMed ID: 22348148
  • DiMauro S. et al. 1981. Science (New York, N.Y.). 212: 1277-9. PubMed ID: 6262916
  • Fermo E. et al. 2012. Molecular genetics and metabolism. 106: 455-61. PubMed ID: 22705348
  • Noel N. et al. 2006. British journal of haematology. 132: 523-9. PubMed ID: 16412025
  • Pey AL. et al. 2013. Biochemistry. 52: 1160-70. PubMed ID: 23336698

Ordering/Specimens

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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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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.
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