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Test ID HEX4 Glucotetrasaccharides, Urine

Advisory Information


Additional Testing Requirements

When requested for the diagnosis of Pompe disease (GSD II), glucose tetrasaccharide concentrations in urine need to be interpreted in light of the clinical presentation and other laboratory tests, such as blood creatine kinase, alpha-glucosidase (GAA) activity, and GAA genotype.

Necessary Information

Patient's age and reason for referral are required.

Specimen Required

Supplies: Aliquot Tube, 5 mL (T465)

Container/Tube: Plastic, 5-mL urine tube (T465)

Specimen Volume: 3 mL

Collection Instructions:

1. Collect a random urine specimen.

2. No preservative.


If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.

Secondary ID


Useful For

Diagnosing Pompe disease, when used in conjunction with acid alpha-glucosidase enzyme activity assays and molecular genetic analysis of the GAA gene


Monitoring Pompe patients on enzyme replacement therapy


May support the diagnosis and monitoring of other glycogen storage disorders; however, glucose tetrasaccharide (Glc4) excretion appears to be less consistently elevated in glycogen storage disorders other than Pompe disease


This test is not useful for carrier screening


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 glycogen storage disorder type II (GSD II, Pompe disease) 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

See Newborn Screen Follow-up for Pompe Disease in Special Instructions.

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

Glucotetrasaccharides, U

Specimen Type


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Urine Frozen (preferred) 87 days
  Refrigerated  28 days
  Ambient  14 days

Reject Due To









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 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.


Pompe disease is caused by mutations in the GAA gene. The classic, early infantile onset variant 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 variants 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 variants 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 outcome in many patients with either classic infantile onset or later onset forms of 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 and molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) 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

≤14 months: ≤14.9 mmol/mol Cr

≥15 months: ≤4.0 mmol/mol Cr


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.


Elevated glucose tetrasaccharide (Glc4) result may be due to dietary artifacts in particular ingestion of carbohydrates.

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;58:1139-1147

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;316:175-180

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:50-58

Day(s) and Time(s) Performed

Wednesday; 11 a.m.

Analytic Time

7 days (Not reported on Saturday or Sunday)

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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 U.S. Food and Drug Administration.

CPT Code Information



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

NY State Approved