Long-term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker.

To investigate the correlation of the urinary glucose tetrasaccharide, Glcalpha1-6Glcalpha1-4Glcalpha1-4Glc, (Glc4) with skeletal muscle glycogen content and the long-term clinical response to enzyme replacement therapy with recombinant human acid alpha glucosidase in infantile Pompe disease. Eighteen patients, < or =6 months old, were enrolled in a clinical trial of enzyme replacement therapy for up to 142 weeks. Urinary Glc4, skeletal muscle glycogen, and other clinical and laboratory assessments were made at baseline and at regular intervals. Urinary Glc4 was determined using an isotope-dilution tandem mass spectrometric assay. The clinical response to treatment was defined according to the motor function response. Trends in urinary Glc4 were correlated with the clinical response and compared with serum enzyme markers of skeletal muscle damage, creatine kinase, aspartate aminotransferase, and alanine aminotransferase. Urinary Glc4, in contrast to the serum markers, correlated closely with skeletal muscle glycogen content and with the clinical response. Patients with the best response to treatment maintained the lowest levels of Glc4 throughout the trial. The results from this study support the use of urinary Glc4 for monitoring patients with infantile-onset Pompe disease on therapy.