Urinary tetraglucoside excretion as a biomarker in liver glycogen storage diseases

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.

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.

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.

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.

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