Test Id : HGEM
Hydroxyglutaric Acids, Glutaric Acid, Ethylmalonic Acid, and Methylsuccinic Acid, Blood Spot
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluation of patients with an abnormal newborn screen showing elevations of glutarylcarnitine (C5-DC) using dried blood spot specimens
Evaluation of patients with abnormal newborn screens showing elevations of C4-acylcarnitine to aid in the differential diagnosis of short-chain acyl-CoA dehydrogenase and isobutyryl-CoA dehydrogenase deficiencies
Diagnosis of glutaric acidemia type 1
Aiding in diagnosis of glutaric acidemia type 2
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
Second-tier newborn screening for follow-up of C4-acylcarnitine and glutarylcarnitine (C5DC) elevations.
Differentiating diagnoses of short-chain Co-A dehydrogenase (SCAD) deficiency, isobutyryl-CoA dehydrogenase (IBDH) deficiency, and ethylmalonic encephalopathy.
Differentiating diagnoses of glutaric acidemia type I (GA-1) and glutaric acidemia type II (GA-2)
Method Name
A short description of the method used to perform the test
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
Ethylmalonic encephalopathy (EE)
Isobutyryl-CoA dehydrogenase (IBDH) deficiency
Glutaric acidemia type 1 (GA-1)
Glutaric academia type 2 (GA-2)
GA 1
GA I
GA1
GAI
GA 2
GA II
GA2
GAII
GCDH (Glutaryl-CoA Dehydrogenase) Deficiency
Blood Spots
Newborn Screening
Multiple acyl-CoA dehydrogenase deficiency (MADD)
Glutaryl-CoA Dehydrogenase (GCDH) deficieny
Specimen Type
Describes the specimen type validated for testing
Whole blood
Necessary Information
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Card-Blood Spot Collection (Filter Paper) from heel or finger stick
Acceptable: PerkinElmer (formerly Ahlstrom 226) filter paper, Munktell filter paper, Whatman Protein Saver 903 paper, available newborn screening card, blood collected in tubes containing sodium heparin or EDTA and dried on filter paper
Specimen Volume: 2 Blood spots
Collection Instructions:
1. Do not use device or capillary tube containing ACD to collect specimen. Sodium heparin or EDTA are acceptable but must be spotted on card the same day as collected.
2. Completely fill at least 2 circles on the filter paper card (approximately 100 microliters blood per circle).
3. Let blood dry on filter paper at room temperature in a horizontal position for a minimum of 3 hours.
4. Do not stack wet specimens.
5. Do not expose specimen to heat or direct sunlight.
6. Keep specimen dry.
Additional Information:
1. For collection instructions, see Blood Spot Collection Instructions.
2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).
3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
1. Biochemical Genetics Patient Information (T602)
2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
1 Blood spot
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Shows serum rings Insufficient specimen Blood collected with ACD Nonapproved filter paper | Reject |
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 |
|---|---|---|---|
| Whole blood | Ambient (preferred) | 123 days | FILTER PAPER |
| Refrigerated | 123 days | FILTER PAPER | |
| Frozen | 123 days | FILTER PAPER |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluation of patients with an abnormal newborn screen showing elevations of glutarylcarnitine (C5-DC) using dried blood spot specimens
Evaluation of patients with abnormal newborn screens showing elevations of C4-acylcarnitine to aid in the differential diagnosis of short-chain acyl-CoA dehydrogenase and isobutyryl-CoA dehydrogenase deficiencies
Diagnosis of glutaric acidemia type 1
Aiding in diagnosis of glutaric acidemia type 2
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
Second-tier newborn screening for follow-up of C4-acylcarnitine and glutarylcarnitine (C5DC) elevations.
Differentiating diagnoses of short-chain Co-A dehydrogenase (SCAD) deficiency, isobutyryl-CoA dehydrogenase (IBDH) deficiency, and ethylmalonic encephalopathy.
Differentiating diagnoses of glutaric acidemia type I (GA-1) and glutaric acidemia type II (GA-2)
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Acylcarnitine analysis is included in newborn screening blood tests and is utilized for detection of several inborn errors of metabolism, including fatty acid oxidation disorders (FAOD) and organic acidemias (OA). A limitation of this analytic method is its inability to differentiate between several isomers. Additional testing of 2-hydroxyglutaric acid (2OH-GA), 3-hydroxyglutaric acid (3OH-GA), glutaric acid (GA), methylsuccinic acid (MSA), and ethylmalonic acid (EMA) by liquid chromatography tandem mass spectrometry allows better differentiation among C4-acylcarnitine and glutarylcarnitine/C10-OH isomers.
C4-acylcarnitine represents both butyrylcarnitine and isobutyrylcarnitine and is elevated in short-chain acyl Co-A dehydrogenase (SCAD) deficiency, isobutyryl-CoA dehydrogenase (IBDH) deficiency, and ethylmalonic encephalopathy (EE). SCAD deficiency is a condition affecting fatty acid metabolism with reported symptoms of hypoglycemia, lethargy, developmental delays, and failure to thrive. There is controversy on whether a biochemical diagnosis necessarily confers clinical symptoms. IBDH deficiency is characterized by cardiomyopathy, hypotonia, and developmental delays, although many individuals with IBDH deficiency are asymptomatic. EE is a rare progressive encephalopathy associated with hypotonia, seizures, and abnormal movements.
Individuals with SCAD deficiency demonstrate elevated plasma EMA and MSA levels and individuals with EE show only elevations in EMA, while individuals with IBDH deficiency do not typically have elevations in either EMA or MSA.
Glutarylcarnitine (C5-DC) is elevated in glutaric acidemia type I (GA1) but is not differentiated from C10-OH acylcarnitine. GA1 is caused by a deficiency of glutaryl-CoA dehydrogenase and is characterized by bilateral striatal brain injury leading to dystonia, often a result of acute neurologic crises triggered by illness. Individuals with GA1 typically show elevations of GA and 3OH-GA, even in those considered to be "low excretors."
Glutaric acidemia type II (GA2), also known as multiple acyl-CoA dehydrogenase deficiency (MADD), is caused by defects in either the electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase. This disease can be severe and is often fatal in the first weeks of life with typical symptoms of hypoglycemia, muscle weakness, metabolic acidosis, dysmorphic features, cardiac defects or arrhythmias, renal cysts, and fatty infiltration of the liver. GA2 can have a milder presentation, also known as ethylmalonic-adipic aciduria, with Reye-like illnesses in childhood and muscle weakness in childhood and adulthood. In addition to elevations in GA, individuals with GA2 can also show increased EMA, MSA, and 2OH-GA.
The American College of Medical Genetics and Genomics Newborn Screening Work Group published diagnostic algorithms for the follow-up of infants who had a positive newborn screening result. For more information see www.acmg.net.
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.
2-OH Glutaric acid: < or =25 nmol/mL
3-OH Glutaric acid: < or =1.5 nmol/mL
Glutaric acid: < or =1.5 nmol/mL
Methylsuccinic acid: < or =0.45 nmol/mL
Ethylmalonic acid: < or =3.5 nmol/mL
Interpretation
Provides information to assist in interpretation of the test results
Elevations of ethylmalonic acid (EMA) and methylsuccinic acid (MSA) are consistent with a diagnosis of short-chain acyl Co-A dehydrogenase (SCAD) deficiency.
Elevation of EMA is consistent with a diagnosis of ethylmalonic encephalopathy.
Normal levels of EMA in the context of elevated C4 is consistent with a diagnosis of isobutyryl-CoA dehydrogenase (IBDH) deficiency.
Elevation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OH-GA) are consistent with a diagnosis of glutaric acidemia type I (GA1).
Elevation of GA, 2-hydroxyglutaric acid (2OH-GA), 3OH-GA, EMA, and MSA are consistent with a diagnosis of glutaric acidemia type II (GA2).
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. Rinaldo P, Cowan TM, Matern D. Acylcarnitine profile analysis. Genet Med. 2008;10(2):151-156
2. Vockley J, Zschocke J, Knerr I, Vockley C, Michael Gibson KK. Branched chain organic acidurias. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed April 1,2025. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225085758
3. Frerman FE, Goodman SI. Defects of electron transfer flavoprotein and electron transfer flavoprotein-ubiquinone oxidoreductase: Glutaric acidemia type II. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed April 1,2025. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225088261
4. Larson A, Goodman S. Glutaric acidemia type 1. In: Adam MP, Mirzaa GM, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2019. Accessed April 1,2025. Available at www.ncbi.nlm.nih.gov/books/NBK546575/
5. Di Meo I, Lamperti C, Tiranti V. Ethylmalonic encephalopathy. In: Adam MP, Mirzaa GM, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2017. Accessed April 1,2025. Available at www.ncbi.nlm.nih.gov/books/NBK453432/
6. Wolfe L, Jethva R, Oglesbee D, Vockley J. Short-chain acyl-CoA dehydrogenase deficiency. In: Adam MP, Mirzaa GM, Pagon RA, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2011. Updated August 9, 2018. Accessed April 1,2025. Available at www.ncbi.nlm.nih.gov/books/NBK63582/
Method Description
Describes how the test is performed and provides a method-specific reference
An aqueous internal standard is added to the specimen. The extract is evaporated and reconstituted prior to injection onto a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. The ratios of the extracted peak areas of glutaric acid, ethylmalonic acid, and methylsuccinic acid to their respective internal standards as determined by LC-MS/MS are used to calculate the concentration of each analyte in the sample.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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, Wednesday
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
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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. It 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.
CPT codes are provided by the performing laboratory.
83918
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| HGEM | HGEM, BS | 92672-5 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 36048 | 2-OH Glutaric acid | 75037-2 |
| 36049 | 3-OH Glutaric acid | 82505-9 |
| 36050 | Glutaric acid | 82504-2 |
| 36051 | Methylsuccinic acid | 82503-4 |
| 36052 | Ethylmalonic acid | 82502-6 |
| 36053 | Interpretation (HGEM) | 59462-2 |
| 36054 | Reviewed By | 18771-6 |