Glucose Phosphate Isomerase Deficiency via the GPI Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8091 | GPI | 81479 | 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.
Clinical Features and Genetics
Clinical Features
Glucose Phosphate Isomerase (GPI) deficiency is the third most common hereditary red blood cell enzyme deficiency behind glucose-6-phosphate dehydrogenase (Test #1259) and pyruvate kinase (Test #1652) deficiencies, but only about 60 cases have been reported to date. Clinical features include nonspherocytic hemolytic anemia which can lead to pallor, jaundice, fatigue, shortness of breath, and tachycardia. Disease severity ranges with bacterial and viral infections potentially triggering episodic periods of hemolytic crisis. In rare cases, patients with GPI deficiency may have ataxia, intellectual disability, splenomegaly, excess iron in blood, and gallstones. Clinical severity ranges from hydrops fetalis resulting in immediate neonatal death to mild hemolytic anemia with diagnosis occurring in early to late childhood (Whitelaw et al. 1979; Baronciani et al. 1996). Treatments for GPI deficiency include blood transfusions and in some cases splenectomy.
Genetics
GPI deficiency is inherited in an autosomal recessive manner through mutations in the GPI gene. The majority of causative variants to date are missense mutations leading to destabilization of the GPI protein and have been found throughout the coding region (Repiso et al. 2006; Xu and Beutler 1994; Kanno et al. 1996; Repiso et al. 2005). Splice site alterations, small deletions, and nonsense mutations have been reported in a minority of cases (Baronciani et al. 1996). To date, no gross deletions of the GPI gene have been documented. GPI functions as a dimeric enzyme and catalyzes the second step of glycolysis, conversion of glucose-6-phosphate to fructose-6-phosphate. The monomeric form of GPI also acts like a cytokine produced by activated T-cells to induce immunoglobulin secretion (Gurney et al. 1986).
Clinical Sensitivity - Sequencing with CNV PGxome
Clinical sensitivity is difficult to assess as no large patient cohorts of GPI deficiency have been studied. In two separate reports, causative mutations in the GPI gene were found in 4 of 4 and 4 of 4 unrelated patients with known biochemical evidence showing impaired GPI function (Baronciani et al 1996; Xu and Beutler 1994).
Testing Strategy
This test provides full coverage of all coding exons of the GPI 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
Ideal candidates have biochemical results indicative of impaired GPI enzymatic activity in erythrocytes, reticulocytosis, and clinical features consistent with GPI deficiency (Xu and Beutler 1994; Blume and Beutler 1972). Patients heterozygous for a pathogenic variant in the GPI gene may have moderate decreases in GPI enzymatic activity but are asymptomatic (Repiso et al. 2006). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GPI.
Ideal candidates have biochemical results indicative of impaired GPI enzymatic activity in erythrocytes, reticulocytosis, and clinical features consistent with GPI deficiency (Xu and Beutler 1994; Blume and Beutler 1972). Patients heterozygous for a pathogenic variant in the GPI gene may have moderate decreases in GPI enzymatic activity but are asymptomatic (Repiso et al. 2006). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GPI.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| GPI | 172400 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hemolytic Anemia, Nonspherocytic, Due To Glucose Phosphate Isomerase Deficiency | AR | 613470 |
Citations
- Baronciani L, Zanella A, Bianchi P, Zappa M, Alfinito F, Iolascon A, Tannoia N, Beutler E, Sirchia G. 1996. Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia. Blood 88: 2306–2310. PubMed ID: 8822952
- Blume KG, Beutler E. 1972. Detection of glucose-phosphate isomerase deficiency by a screening procedure. Blood 39: 685–687. PubMed ID: 5022716
- Gurney ME, Heinrich SP, Lee MR, Yin HS. 1986. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science 234: 566–574. PubMed ID: 3764429
- Repiso A, Oliva B, Vives-Corrons J-L, Beutler E, Carreras J, Climent F. 2006. Red cell glucose phosphate isomerase (GPI): a molecular study of three novel mutations associated with hereditary nonspherocytic hemolytic anemia. Human Mutation 27: 1159–1159. PubMed ID: 17041899
- Repiso A, Oliva B, Vivescorrons J, Carreras J, Climent F. 2005. Glucose phosphate isomerase deficiency: enzymatic and familial characterization of Arg346His mutation. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1740: 467–471. PubMed ID: 15949716
- Whitelaw AG, Rogers PA, Hopkinson DA, Gordon H, Emerson PM, Darley JH, Reid C, Crawfurd M d’A. 1979. Congenital haemolytic anaemia resulting from glucose phosphate isomerase deficiency: genetics, clinical picture, and prenatal diagnosis. Journal of medical genetics 16: 189–196. PubMed ID: 469896
- Xu W, Beutler E. 1994. The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia. Journal of Clinical Investigation 94: 2326. PubMed ID: 7989588
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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2) Select Additional Test Options
No Additional Test Options are available for this test.