Test Catalog

Test Id : 2HGA

2-Hydroxyglutaric Acid Chiral Analysis, Quantitative, Random, Urine

Useful For
Suggests clinical disorders or settings where the test may be helpful

Determining type of 2-hydroxyglutaric aciduria by chiral analysis of urine

Highlights

This test provides differentiation of the 3 subtypes of 2-hydroxyglutaric aciduria: D-2-hydroxyglutaric aciduria, L-2-hydroxyglutaric aciduria, and combined D,L-2-hydroxyglutaric aciduria. It also provides a quantitative result of the D- and L-enantiomers of 2-hydroxyglutaric acid via gas chromatography-mass spectrometry analysis.

Method Name
A short description of the method used to perform the test

Gas Chromatography-Mass Spectrometry (GC-MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

D-,L- 2-Hydroxyglutaric Acid, QN, U

Aliases
Lists additional common names for a test, as an aid in searching

2-hydroxyglutaric aciduria

2-HGA

2HGA

2OHGA

2-OHGA

L-2-Hydroxyglutaric aciduria

D-2-Hydroxyglutaric aciduria

Combined D-2 and L-2 hydroxyglutaric aciduria

D, L-2-hydroxyglutaric aciduria

Specimen Type
Describes the specimen type validated for testing

Urine

Necessary Information

Age and sex of patient are required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Urine Tube, 10 mL (T068)

Container/Tube: Plastic, 10-mL urine tube

Specimen Volume: 10 mL

Pediatric: If the collection volume appears insufficient, submit as much specimen as possible in a single container; the laboratory will determine if volume is sufficient for test.

Collection Instructions:

1. Collect a random urine specimen (first morning void preferred)

2. No preservative

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

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

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Urine Frozen (preferred) 416 days
Ambient 14 days
Refrigerated 14 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Determining type of 2-hydroxyglutaric aciduria by chiral analysis of urine

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

2-Hydroxyglutaric aciduria disorders are a group of cerebral organic acidurias that present biochemically with an elevation of 2-hydroxyglutaric acid (2-HGA) in the urine. There are 2 enantiomers or forms of 2-HGA, the D-form and the L-form. Depending on the genetic defect, individuals may have an elevation of one or both forms of 2-HGA. Routine organic acid analysis (OAU / Organic Acids Screen, Random, Urine), while able to detect 2-HGA, is unable to distinguish between the 2 enantiomers; however, they can be separated with this more specialized biochemical test.

 

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 (MRI) 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 (D-2-HG) 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).

 

Combined D,L-2-hydroxylglutaric aciduria (D,L-2-HGA) is the most severe of the 3 types and is 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.

 

Molecular genetic testing is available (2OHGP / 2-Hydroxyglutaric Aciduria Gene Panel, Varies), which includes analysis of D2HGDH, L2HGDH, IDH2, and SLC25A1 and can be used to confirm abnormal urine results.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Age

D-2-hydroxyglutaric acid (mmol/mol creatinine)

L-2-hydroxyglutaric acid
(mmol/mol creatinine)

0-11 months

< or =14.11

< or =17.38

12-23 months

< or =13.76

< or =17.03

24-35 months

< or =13.38

< or =16.63

3 years

< or =12.96

< or =16.18

4 years

< or =12.20

< or =15.35

5 years

< or =11.40

< or =14.44

6 years

< or =10.56

< or =13.46

7 years

< or =9.71

< or =12.43

8 years

< or =8.93

< or =11.44

9 years

< or =8.21

< or =10.50

10 years

< or =7.56

< or =9.66

11 years

< or =6.99

< or =8.94

12 years

< or =6.47

< or =8.33

13 years

< or =6.01

< or =7.83

14 years

< or =5.60

< or =7.44

15 years

< or =5.23

< or =7.14

16 years

< or =4.91

< or =6.93

17 years

< or =4.63

< or =6.78

18 years

< or =4.40

< or =6.69

19 years

< or =4.21

< or =6.63

20 years

< or =4.07

< or =6.60

21 years

< or =3.96

< or =6.59

22 years

< or =3.88

< or =6.58

23 years

< or =3.81

< or =6.56

24 years

< or =3.76

< or =6.54

25 years

< or =3.71

< or =6.50

26 years

< or =3.67

< or =6.44

27 years

< or =3.63

< or =6.37

28 years

< or =3.59

< or =6.27

29 years

< or =3.56

< or =6.15

30 years

< or =3.54

< or =6.02

31 years

< or =3.52

< or =5.87

32 years

< or =3.50

< or =5.72

33 years

< or =3.49

< or =5.57

34 years

< or =3.48

< or =5.41

35 years

< or =3.46

< or =5.26

36 years

< or =3.45

< or =5.13

37 years

< or =3.43

< or =5.00

38 years

< or =3.42

< or =4.88

39 years

< or =3.40

< or =4.78

40 years

< or =3.39

< or =4.70

41 years

< or =3.37

< or =4.62

42 years

< or =3.35

< or =4.55

43 years

< or =3.33

< or =4.50

44 years

< or =3.30

< or =4.44

45 years

< or =3.28

< or =4.40

46 years

< or =3.24

< or =4.35

47 years

< or =3.21

< or =4.31

48 years

< or =3.17

< or =4.27

49 years

< or =3.13

< or =4.23

50 years

< or =3.10

< or =4.19

51 years

< or =3.07

< or =4.16

52 years

< or =3.04

< or =4.12

53 years

< or =3.01

< or =4.10

54 years

< or =2.99

< or =4.07

55 years

< or =2.97

< or =4.04

56 years

< or =2.95

< or =4.01

57 years

< or =2.93

< or =3.98

58 years

< or =2.91

< or =3.94

59 years

< or =2.89

< or =3.91

60 years

< or =2.87

< or =3.87

61 years

< or =2.85

< or =3.84

62 years

< or =2.83

< or =3.80

63 years

< or =2.79

< or =3.78

64 years

< or =2.76

< or =3.75

65 years

< or =2.71

< or =3.73

66 years

< or =2.67

< or =3.72

67 years

< or =2.61

< or =3.71

68 years

< or =2.56

< or =3.69

69 years

< or =2.50

< or =3.68

70 years

< or =2.44

< or =3.66

71 years

< or =2.38

< or =3.64

72 years

< or =2.32

< or =3.61

73 years

< or =2.26

< or =3.56

74 years

< or =2.21

< or =3.50

75 years

< or =2.16

< or =3.43

76 years

< or =2.10

< or =3.35

77 years

< or =2.05

< or =3.26

78 years

< or =2.00

< or =3.17

79 years

< or =1.94

< or =3.08

80 years

< or =1.89

< or =2.99

81 years

< or =1.84

< or =2.91

82 years

< or =1.80

< or =2.84

83 years

< or =1.75

< or =2.78

84 years

< or =1.71

< or =2.73

85 years

< or =1.68

< or =2.69

86 years

< or =1.65

< or =2.67

87 years

< or =1.64

< or =2.65

88 years

< or =1.63

< or =2.64

> or =89 years

< or =1.62

< or =2.64

Interpretation
Provides information to assist in interpretation of the test results

The values for the D-2-hydroxyglutaric acid and L-2-hydroxyglutaric acid concentrations are reported. The interpretation of the result must be correlated with clinical and other laboratory findings.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

No significant cautionary statements

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C: Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012 Jul;35(4):571-587. doi: 10.1007/s10545-012-9462-5

2. Muhlhausen C, Salomons GS, Lukacs Z, et al: Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment. J Inherit Metab Dis. 2014 Sep;37(5):775-781. doi: 10.1007/s10545-014-9702-y

3. Struys EA: D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. J Inherit Metab Dis. 2006 Feb;29(1):21-29. doi: 10.1007/s10545-006-0317-9

4. Perales-Clemente E, Hewitt AL, Studinski AL, et al: Bilateral subdural hematomas and retinal hemorrhages mimicking nonaccidental trauma in a patient with D-2-hydroxyglutaric aciduria. JIMD Rep. 2020 Nov 20;58(1):21-28. doi: 10.1002/jmd2.12188

Method Description
Describes how the test is performed and provides a method-specific reference

Urine volumes are spiked with a mixture of internal standards and evaporated. The dry residue is derivatized to form the diastereomeric molecules, then acidified and extracted. After evaporation, the dry residue is derivatized esters at the carboxylic acid moiety. Specimens are then analyzed by capillary gas chromatography mass spectrometry (GC/MS) selected ion monitoring using chemical ionization, with chromatographic separation of the L,L- and D,L-diastereoisomers of derivatized 2-hydroxyglutaric acid (2-HGA), corresponding to L-2-HGA and D-2-HGA, respectively.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 9 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83921 x 2

LOINC® Information

Test Id Test Order Name Order LOINC Value
2HGA D-,L- 2-Hydroxyglutaric Acid, QN, U 79297-8
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
614619 Interpretation 79303-4
614620 D-2-Hydroxyglutaric acid 80100-1
614621 L-2-Hydroxyglutaric acid 80099-5
614622 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports