Test Code 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)

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.

Special Instructions

Reporting Name

2-OH Glutaric Aciduria Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

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.

Specimen Retention Time

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months; Blood spots/Saliva: 1 month

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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