Test Catalog

Test Id : GSH

Glutathione, Blood

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

Evaluation of neonatal hyperbilirubinemia, favism or chronic or episodic hemolysis or jaundice

 

Evaluation for gamma-glutamylcysteine synthetase deficiency (OMIM 230450)

 

Evaluation for glutathione synthetase deficiency causing hemolytic anemia (OMIM 231900)

 

Evaluation for generalized glutathione synthetase deficiency with 5-oxoprolinuria (OMIM 266130)

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

Kinetic Spectrophotometry

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

Glutathione, B

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

Glutathione Synthase

Reduced Glutathione, Blood

Specimen Type
Describes the specimen type validated for testing

Whole Blood ACD-B

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

Collection Container/Tube:

Preferred: Yellow top (ACD solution B)

Specimen Volume: 6 mL

Collection Instructions: Send specimen in original tube. Do not transfer blood to other containers.

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

Gross hemolysis 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 ACD-B Refrigerated (preferred) 20 days

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

Evaluation of neonatal hyperbilirubinemia, favism or chronic or episodic hemolysis or jaundice

 

Evaluation for gamma-glutamylcysteine synthetase deficiency (OMIM 230450)

 

Evaluation for glutathione synthetase deficiency causing hemolytic anemia (OMIM 231900)

 

Evaluation for generalized glutathione synthetase deficiency with 5-oxoprolinuria (OMIM 266130)

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

Hemolytic anemia may be associated with deficiency of erythrocyte enzymes. Red blood cell (RBC) enzymes linked to hemolysis are those important in the energy generation of glycolysis or protection from oxidative stress such as the hexose monophosphate shunt.

 

The hexose monophosphate pathway depends primarily upon the glucose 6-phosphate dehydrogenase (G6PD) enzyme for the generation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) with 6-phosphogluconate dehydrogenase (6PGD) providing an additive effect. Both reactions require adequate levels of reduced glutathione (GSH). Because RBCs lack the citric acid cycle, this is an important source of NADPH, and a deficiency of G6PD or GSH results in the inability to neutralize oxidative insults. GSH is synthesized from amino acids by two enzymatic steps and is present in liver, kidney, brain, muscle, and RBCs. It plays widely versatile and important roles in the synthesis of proteins and DNA, the processing of medications and toxins, and other redox reactions.

 

Similar to G6PD deficiency, glutathione deficiency can have an episodic acute time course of hemolysis or jaundice, be triggered by fava beans, and cause neonatal hyperbilirubinemia. Five enzymes impact GSH availability and therefore are potential candidates for abnormalities leading to glutathione deficiency:

-Two enzymes, gamma-glutamylcysteine synthetase (GCLC) and glutathione synthetase (GSS), are required for GSH synthesis

-Two enzymes, glutathione reductase (GSR) and glutathione peroxidase (GPX1), are required for reduction-oxidation cycling of oxidized glutathione (GSSG) to reduced glutathione (GSH)

-A family of enzymes, glutathione S-transferases (GSTs), utilizes GSH in the detoxification and preparation of substances for excretion into the bile or urine

 

Enzyme deficiencies have been reported in all of these enzymes, albeit very rarely. The best characterized are GSS and GCLC deficiencies. GSS deficiency is associated with two clinical presentations; a mild form causing isolated chronic hemolytic anemia (OMIM 231900), and a more severe form marked by urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia, and central nervous system disorders (5-oxoprolinuria, OMIM 266130). GCLC deficiency is associated with moderate to severe chronic hemolytic anemia present from neonatal or early childhood, or compensated hemolysis with sporadic but recurrent anemia or jaundice. Some cases have shown learning disabilities, severe and progressive ataxia with myopathy and spinocerebellar degeneration. GSR deficiency has been confirmed in three siblings with favism (episodic hemolysis after fava bean ingestion) and cataracts in early adulthood, and an unrelated infant with marked neonatal hyperbilirubinemia. GSR activity can be decreased in riboflavin deficiency, but whether this results in hemolysis is not clear. Although patients have been reported with anemia in the context of decreased GPX1 activity (OMIM 614164) and decreased GST activity was found in a person with hemolytic anemia, splenomegaly, hyperbilirubinemia, and cholelithasis, neither have been characterized sufficiently as the definitive cause of hemolysis. All described cases have shown autosomal recessive inheritance pattern.

 

A deficiency of either of the synthetic enzymes, GCLC or GSS, results in GSH levels less than 25%, but many show a virtual absence of measurable GSH. Heterozygotes usually show normal GSH levels. Elevated concentrations of GSH are found in patients with myelofibrosis and in those with pyrimidine-5'-nucleotidase deficiency.

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.

> or =12 months: 46.9-90.1 mg/dL RBC

Reference values have not been established for patients who are <12 months of age.

Interpretation
Provides information to assist in interpretation of the test results

Measurement of reduced glutathione (GSH) is used as a surrogate for the activity of the enzymes that contribute to normal levels of GSH within the red blood cell. GSH is associated with less than 25% of mean normal in individuals with deficiencies of gamma-glutamyl cysteine synthetase or glutathione synthetase.

 

Elevated concentrations of GSH are of uncertain significance. This finding can be nonspecific and is seen in normal neonates, pyrimidine-5’-nucleotidase deficiency, lead poisoning, dyserythropoietic disorders (inherited and acquired), myelofibrosis (possibly due to chromosome 8 duplication), or riboflavin supplementation. Consistently elevated glutathione levels have been reported in a family with mild hemolytic anemia of uncertain cause (1); however, whether this was causative or incidental was not determined.

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

Samples with white blood cell counts greater than 20x10(9)/L have been shown to falsely increase the glutathione level by as much as 25%. Results in the normal or elevated range should be interpreted with caution if high white blood cell count is noted.

 

Recent transfusion may mask the patient's intrinsic enzyme activity and cause unreliable results.

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

1. Valentine WN, Paglia DE: Syndromes with increased red cell glutathione (GSH). Hemoglobin. 1980;4(5-6):799-804. doi: 10.3109/03630268008997748

2. Manu Pereira M, Gelbart T, Ristoff E, et al: Chronic non-spherocytic hemolytic anemia associated with severe neurological disease due to gamma-glutamylcysteine synthetase deficiency in a patient of Moroccan origin. Haematologica. 2007 Nov;92(11). doi: 10.3324/haematol.11238

3. Ristoff E, Mayatepek E, Larsson A: Long-term clinical outcome in patients with glutathione synthetase deficiency. J Pediatr. 2001 Jul;139(1):79-84. doi: 10.1067/mpd.2001.114480

4. Konrad PN, Richards F, Valentin WN, et al: Gamma glutamyl cysteine synthetase deficiency. N Engl J Med. 1972;286:557

5. Mehta A, Mason PJ, Vulliamy TJ: Glucose-6-phosphate dehydrogenase deficiency. Baillieres Best Pract Res Clin Haematol. 2000 Mar;13(1):21-38

6. Beutler E, Dunning D, Dabe IB, Forman L: Erythrocyte glutathione S-transferase deficiency and hemolytic anemia. Blood. 1988;72:73-77

7. Kamerbeek NM, van Zwieten R, de Boer M, et al: Molecular basis of glutathione reductase deficiency in human blood cells. Blood. 2007 Apr 15;109(8):3560-3566. doi: 10.1182/blood-2006-08-042531

8. Tomoda A, Noble NA, Lachant NA, Tanaka KR: Hemolytic anemia in hereditary pyrimidine 5'-nucleotidase deficiency: nucleotide inhibition of G6PD and the pentose phosphate shunt. Blood. 1982 Nov;60(5):1212-1218

9. van Solinge WW, van Wijk: Enzymes of the red blood cell. In: Rifai N, Horvath AR, Wittwer CT: eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:chap 30

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

Virtually all of the non-protein sulfhydryl of red cells is in the form of reduced glutathione (GSH). 5,5'-dithiobis (2-nitrobenzoic acid) is a disulfide compound, which is readily reduced by sulfhydryl compounds, forming a highly colored yellow anion. The absorbance of this resultant yellow substance is measured by 412 nm and compared to that of a known standard.(Beutler E: Red cell metabolism. In: A Manual of Biochemical Methods. 2nd ed. Grune and Stratton, 1984; Alisik M, Neselioglu S, Erel O: A colorimetric method to measure oxidized, reduced and total glutathione levels in erythrocytes, J Lab Med. 2019:43(5), 269-277. doi: 10.1515/labmed-2019-0098)

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 through Friday

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.

10 to 13 days

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

28 days

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.

82978

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