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HelpTest Code HEX4 Glucotetrasaccharides, Random, Urine
Reporting Name
Glucotetrasaccharides, UUseful For
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
For more information see Newborn Screen Follow-up for Pompe Disease
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
UrineOrdering Guidance
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.
Specimen Required
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.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Urine | Frozen (preferred) | 87 days | |
| Refrigerated | 28 days | ||
| Ambient | 14 days |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Special Instructions
Reference Values
≤14 months: ≤14.9 mmol/mol Cr
≥15 months: ≤4.0 mmol/mol Cr
Day(s) Performed
Wednesday
CPT Code Information
82542
82570
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| HEX4 | Glucotetrasaccharides, U | 53868-6 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 64174 | Glucotetrasaccharides, U | 53868-6 |
| BG710 | Reason for Referral | 42349-1 |
| BA2896 | Intepretation (HEX4) | 59462-2 |
| BA2897 | Reviewed By | 18771-6 |
Forms
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Secondary ID
64174Highlights
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.
Clinical Information
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.
Interpretation
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
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
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
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)