Test Catalog

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 Pompe patients 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.

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

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.


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 outcome 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 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

Elevated glucotetrasaccharide (Glc4) result may be due to dietary artifacts particularly ingestion of carbohydrates.

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;58:1139-1147

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

Special Instructions Library of PDFs including pertinent information and forms related to the test