Test Id : HEX4
Glucotetrasaccharides, Random, Urine
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing Pompe disease, when used in conjunction with acid alpha-glucosidase enzyme activity assays and molecular genetic analysis of the GAA gene
Monitoring patients with Pompe disease on enzyme replacement therapy
May support the diagnosis and monitoring of other glycogen storage disorders; however, glucotetrasaccharide (Glc4) excretion appears to be less consistently elevated in glycogen storage disorders other than Pompe disease
This test is not useful for carrier screening.
Highlights
Increased accumulation of glycogen in the lysosome is a typical finding due to lack of the lysosomal enzyme acid alpha-glucosidase (GAA). Excess glycogen is degraded to glucotetrasaccharide, which is excreted in urine.
Most individuals with Pompe disease (glycogen storage disorder type II: GSD II,) and other glycogen storage disorders excrete glucotetrasaccharides in their urine.
Measuring glucotetrasaccharide in the urine can be helpful when employed in conjunction with GAA enzyme activity assay and molecular genetic analysis of the GAA gene.
Measuring glucotetrasaccharide in the urine of GSD II patients undergoing enzyme replacement therapy (ERT) has been reported as a useful tool for monitoring the effects of treatment.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For more information see Newborn Screen Follow-up for Pompe Disease
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
Glucotetrasaccharides
Glucose tetrasaccharides
Glc4
Hexose tetrasaccharide
Hex4
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For more information see Newborn Screen Follow-up for Pompe Disease
Specimen Type
Describes the specimen type validated for testing
Urine
Additional Testing Requirements
When requested for the diagnosis of Pompe disease (glycogen storage disorder type II), urine glucotetrasaccharide concentrations need to be interpreted in light of the clinical presentation and other laboratory test results, such as blood creatine kinase, alpha-glucosidase (GAA) activity, and GAA genotype.
Necessary Information
1. Patient's age is required.
2. Reason for testing is required.
ORDER QUESTIONS AND ANSWERS
| Question ID | Description | Answers |
|---|---|---|
| BG710 | Reason for Referral |
Rule out Pompe disease Rule out GSDs other than Pompe disease Follow-up of abnormal newborn screening Follow-up of known Pompe patient Not provided |
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Container/Tube: Plastic, 5-mL urine tube
Specimen Volume: 3 mL
Collection Instructions:
1. Collect a random urine specimen.
2. No preservative.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
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 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
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) | 87 days | |
| Ambient | 14 days | ||
| Refrigerated | 28 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing Pompe disease, when used in conjunction with acid alpha-glucosidase enzyme activity assays and molecular genetic analysis of the GAA gene
Monitoring patients with Pompe disease on enzyme replacement therapy
May support the diagnosis and monitoring of other glycogen storage disorders; however, glucotetrasaccharide (Glc4) excretion appears to be less consistently elevated in glycogen storage disorders other than Pompe disease
This test is not useful for carrier screening.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For more information see Newborn Screen Follow-up for Pompe Disease
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid alpha-glucosidase (GAA). This leads to an accumulation of glycogen in the lysosome causing swelling, cell damage, and progressive organ dysfunction. In glycogen storage diseases, excess glycogen is degraded to glucotetrasaccharide (glucose tetrasaccharide: Glc4), which is excreted in urine. Measurement of Glc4 in urine is used for both initial diagnosis and monitoring of patients with Pompe disease and may also be elevated in other glycogen storage disorders.
Pompe disease is caused by deleterious variants in the GAA gene. The classic, early infantile onset form of the disease is characterized by progressive muscle hypotonia, weakness, hypertrophic cardiomyopathy, and death due to either cardiorespiratory or respiratory failure, typically by the end of the first year of life. Juvenile and adult-onset forms of Pompe disease are characterized by later onset and longer survival. Primary symptoms of later-onset Pompe disease include muscle weakness and respiratory insufficiency, with cardiomyopathy only rarely developing. Based on data from newborn screening, the incidence is approximately 1 in 20,000 live births with most patients being affected with later onset forms of Pompe disease. The clinical phenotype depends on residual enzyme activity, with complete loss of activity causing onset in infancy.
Enzyme replacement therapy (ERT) improves outcomes in many patients with either classic infantile-onset or later-onset Pompe disease. Early initiation of treatment improves the prognosis and makes early diagnosis of Pompe disease desirable. Because of this, newborn screening for Pompe disease has recently been added to the Recommended Uniform Screening Panel and already been implemented in some states.
Historically, diagnostic testing required a skin or muscle biopsy to measure GAA enzyme activity. Today, noninvasive enzyme assays (GAAW / Acid Alpha-Glucosidase, Leukocytes) and molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis, Varies) are available for testing in blood and dried blood spots. In addition, Glc4 can be measured in urine to support a diagnosis of Pompe disease and other glycogen storage disorders.
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 =14 months: < or =14.9 mmol/mol Cr
> or =15 months: < or =4.0 mmol/mol Cr
Interpretation
Provides information to assist in interpretation of the test results
An elevated excretion of glucotetrasaccharide is indicative of Pompe disease or other glycogen storage disorders.
Enzyme or molecular analysis is required to confirm suspected diagnosis.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
An elevated glucotetrasaccharide (Glc4) result may be due to dietary artifacts, particularly ingestion of carbohydrates.
Normal glucotetrasaccharide (Glc4) levels may be seen in patients with late-onset Pompe disease.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Sluiter W, van den Bosch JC, Goudriann DA, et al. Rapid ultraperformance liquid chromatography-tandem mass spectrometry assay for a characteristic glycogen-derived tetrasaccharide in Pompe disease and other glycogen storage diseases. Clin Chem. 2012;58(7):1139-1147
2. Young S, Stevens RD, An Y, et al. Analysis of a glucose tetrasaccharide elevated in Pompe disease by stable isotope dilution–electrospray ionization tandem mass spectrometry. Anal Biochem. 2003;316(2):175-180
3. Chien YH, Goldstein JL, Hwu WL, et al. Baseline urinary glucose tetrasaccharide concentrations in patients with infantile- and late-onset Pompe disease identified by newborn screening. JIMD Rep. 2015;19:67-73
4. Young SP, Piraud M, Goldstein, JL, et al. Assessing disease severity in Pompe disease: the roles of a urinary glucose tetrasaccharide biomarker and imaging techniques. Am J Med Genet C Semin Med Genet. 2012;160C(1):50-58
5. Morales-Vila A, Corbalan-Rivas A, Carnero-Gregorio M, et al. Biomarkers in glycogen storage diseases: an update. Int. J Mol Sci. 2021;22(9):4381. doi:10.3390/ijms22094381
Method Description
Describes how the test is performed and provides a method-specific reference
A random urine sample is corrected per creatinine content. The creatinine-corrected urine is combined with ammonium hydroxide and internal standard in a 96-well filter plate. After centrifugation, an aliquot of the eluate is injected onto an amide column and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) in negative mode. The ratio of the extracted peak area for glucotetrasaccharide to the internal standard is used to calculate the concentration of glucotetrasaccharide present.(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.
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 :
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.
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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.
82542
82570
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 |
|---|---|---|
| HEX4 | Glucotetrasaccharides, U | 53868-6 |
| 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.
|
|---|---|---|
| 64174 | Glucotetrasaccharides, U | 53868-6 |
| BG710 | Reason for Referral | 42349-1 |
| BA2896 | Intepretation (HEX4) | 59462-2 |
| BA2897 | Reviewed By | 18771-6 |