AB067. Glucose tetrasaccharide (Glc4) level in urine sample as a biomarker for Pompe patients

Abstract: Pompe disease is a lysosomal storage disease caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase (GAA) enzyme. Our team has started newborn screening of Pompe disease since 2008. Until now, around 800,000 newborns have been screening. Rapid diagnostic criteria for the newborns with infantile-onset Pompe disease (IOPD) has been established by our team. Through this effective program, IOPD infants can receive their first ERT within 4 hours of admission and at an average of 11.56±3.4 days of age. However, for late onset Pompe disease (LOPD) newborns, it is very difficult to distinguish them from the newborns with low GAA enzyme activity caused pseudo-deficiency allele (G576S) by clinical manifestations or enzyme activity. Therefore, we try to find a reliable biomarker to distinguish LOPD newborns from pseudo-deficiency. In this study, we analyzed urinary Glc4 levels of the newborns who have pseudo-deficiency (G576S), suspected LOPD (suspected by their genotypes), or IOPD. We found that all the pseudo-deficiency newborns and suspected LOPD newborns had normal urinary Glc4 level, while IOPD had very high urinary Glc4 level before they got ERT. The urinary Glc4 level decreased rapidly after ERT in these IOPD newborns. For long-term ERT follow up, the urinary Glc4 level elevated gradually after longer-term follow-up in some patients, especially in who received ERT later. We also found that urinary Glc4 level was correlated with serum creatine kinase (CK) level in our patients. Our data suggested that urinary Glc4 level is a good biomarker for IOPD newborns, but not LOPD, especially for the pre-symptomatic LOPD patients.

Keywords: Pompe disease; glucose tetrasaccharide (Glc4); infantile-onset Pompe disease (IOPD); late onset Pompe disease (LOPD); pseudo-deficiency