Urinary tetraglucoside excretion as a biomarker in liver glycogen storage diseases.

INTRODUCTION

Increased urinary tetraglucoside (Glc4) excretions are associated with abnormal glycogen metabolism. While Glc4 is an established biomarker for glycogen storage disease (GSD) type II, a traditional muscle GSD, little data is available on excretions in liver GSD.

METHODS

A single-center retrospective analysis was conducted on urinary Glc4 samples obtained during routine clinical care of 99 individuals with liver GSD, including 9 patients with Glc4 samples taken as part of the diagnostic work-up (i.e., before treatment) and 5 patients with Glc4 samples after liver transplantation.

RESULTS

Glc4 excretions were increased at time of diagnosis in 1/1 GSD IIIa, 3/3 GSD IXa, 1/2 GSD IXa female carrier, 0/1 GSD IXb and 2/2 Fanconi-Bickel syndrome patients. In 8/9 of these patients with samples in the diagnostic work-up, subsequent follow-up samples were available, displaying that Glc4 excretions decreased after initiation of GSD management in 8/8 patients, and in 6/8 patients Glc4 excretions were within the reference range on last follow-up. Analysis of Glc4 samples in the monitoring phase revealed that, despite management, Glc4 excretions were elevated in the majority of GSD Ia (17/27) and Ib (6/10), and all GSD IIIa (19/19), GSD IIIb (4/4), and IXc (1/1) patients. In contrast, increased Glc4 excretions were less frequently observed in GSD IV (1/6), GSD VI (1/2), IXa (4/19), IXa female carrier (0/1), IXb (0/2), and Fanconi-Bickel syndrome (2/4) patients during clinical follow-up. After liver transplantation in a GSD Ia and a GSD Ib patient, Glc4 excretions normalized.

CONCLUSION

Urinary Glc4 may be a useful additional biomarker in liver GSD patients, both in the diagnostic work-up and in the monitoring phase. Future studies could additionally assess the role of Glc4 as response biomarker in drug development.

TAKE-HOME MESSAGE: Urinary Glc4 may be a useful additional biomarker in liver GSD patients, both in the diagnostic work-up and in the monitoring phase.