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HelpTest ID: 2OHGP 2-Hydroxyglutaric Aciduria Gene Panel, Varies
Ordering Guidance
The recommended first-tier test for 2-hydroxyglutaric aciduria is urine organic acids; order OAU / Organic Acids Screen, Random, Urine.
Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblast
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card
Specimen Volume: 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Due to lower concentration of DNA yielded from blood spots, it is possible that additional specimen may be required to complete testing.
2. For collection instructions, see Blood Spot Collection Instructions.
3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).
4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Useful For
Follow up for abnormal biochemical results suggestive of 2-hydroxyglutaric aciduria
Establishing a molecular diagnosis for patients with 2-hydroxyglutaric aciduria
Identifying variants within genes known to be associated with 2-hydroxyglutaric aciduria, allowing for predictive testing of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 4 genes associated with 2-hydroxyglutaric aciduria: D2HGDH, IDH2, L2HGDH, SLC25A1. See Targeted Genes and Methodology Details for 2-Hydroxyglutaric Aciduria Gene Panel in Special Instructions and Method Description for additional details.
Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for 2-hydroxyglutaric aciduria.
Additional first tier testing may be considered/recommended. For more information see Ordering Guidance.
Reporting Name
2-OH Glutaric Aciduria Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
The 2-hydroxyglutaric aciduria disorders are a group of cerebral organic acidurias that present biochemically with an elevation of 2-hydroxyglutaric acid (2-HG) in the urine. There are two enantiomers or forms of 2-hydroxyglutaric acid, the D-form and the L-form. Depending on the genetic defect, individuals may have an elevation of one or both forms of 2-HG. Routine organic acid analysis (OAU / Organic Acids Screen, Random, Urine), while able to detect 2-HG, is unable to distinguish between the two enantiomers; however, they can be separated with more specialized biochemical testing.
L-2-hydroxyglutaric aciduria (L-2-HGA) is caused by defects in L2HGDH and is characterized by progressive cerebellar ataxia and intellectual disability, seizures, and macrocephaly beginning in infancy or early childhood. Symptoms worsen over time leading to severe disability by early adulthood. Magnetic resonance imaging findings include subcortical leukoencephalopathy, generalized cerebellar and cerebral atrophy, and atrophy of the corpus callosum.
D-2-hydroxylglutaric aciduria (D-2-HGA) is characterized by elevated levels of D-2-hydroxyglutaric acid and typically manifests with developmental delay, seizures, and hypotonia, though can vary widely from asymptomatic to severe. There are 2 types of D-2-HGA depending on the genetic cause. D-2-HGA can either be autosomal recessive, resulting from variants in D2HGDH causing reduced enzymatic activity (Type I) or autosomal dominant gain-of-function variants in IDH2 causing overproduction of D-2-HG (Type II).
D,L-2-hydroxylglutaric aciduria is the most severe of the 3 and caused by defects in SLC25A1, which encodes the mitochondrial citrate carrier. It is characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Because of the genetic heterogeneity of the 2-hydroxyglutaric acidurias and the specialized biochemical testing needed to distinguish among the conditions, this genetic panel, which incorporates D2HGDH, L2HGDH, IDH2, and SLC25A1, is an efficient way to diagnose these conditions.
Reference Values
An interpretive report will be provided.
Interpretation
All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424
2. Nota B, Struys EA, Pop A, et al: Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet. 2013;92:627-631. doi: 10.1016/j.ajhg.2013.03.009
3. Kranendijk M, Struys EA, van Schaftingen E, et al: IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science. 2010 Oct 15;330(6002):336. doi: 10.1126/science.1192632
4. Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C: Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012;35(4):571-587. doi: 10.1007/s10545-012-9462-5
5. Pop A, Struys EA, Jansen EEW, et al: D-2-hydroxyglutaric aciduria Type I: functional analysis of D2HGDH missense variants. Hum Mutat. 2019; 40(7):975-982. doi: 10.1002/humu.23751
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| 2OHGP | 2-OH Glutaric Aciduria Gene Panel | 105341-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 608764 | Test Description | 62364-5 |
| 608765 | Specimen | 31208-2 |
| 608766 | Source | 31208-2 |
| 608767 | Result Summary | 50397-9 |
| 608768 | Result | 82939-0 |
| 608769 | Interpretation | 69047-9 |
| 608770 | Resources | 99622-3 |
| 608771 | Additional Information | 48767-8 |
| 608772 | Method | 85069-3 |
| 608773 | Genes Analyzed | 48018-6 |
| 608774 | Disclaimer | 62364-5 |
| 608775 | Released By | 18771-6 |
Day(s) Performed
Varies
Report Available
28 to 42 daysMethod Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.