Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease

Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy caused by acid alpha-glucosidase deficiency, leading to glycogen accumulation in skeletal muscle. Reliable biomarkers for monitoring disease progression and treatment response are lacking. Urinary glucose tetrasaccharide (Glc4), a m...

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Authors: Dominguez-González, C, Iannucci, D, Clark, J, Martin-Jiménez, P, Hold, S, Oliva, P, Bischinger, A, Gallardo, E, Diaz-Manera, J
Format: article
Status:Published version
Publication Date:2026
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p21151
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21151
Access Level:Open access
Keyword:Pompe disease
Glucose tetrasaccharide
Biomarker
Enzymatic replacement therapy
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spelling Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe diseaseDominguez-González, CIannucci, DClark, JMartin-Jiménez, PHold, SOliva, PBischinger, AGallardo, EDiaz-Manera, JPompe diseaseGlucose tetrasaccharideBiomarkerEnzymatic replacement therapyLate-onset Pompe disease (LOPD) is a progressive metabolic myopathy caused by acid alpha-glucosidase deficiency, leading to glycogen accumulation in skeletal muscle. Reliable biomarkers for monitoring disease progression and treatment response are lacking. Urinary glucose tetrasaccharide (Glc4), a marker of glycogen turnover, is well established in infantile-onset Pompe disease, but its prognostic value in LOPD under longitudinal real-world conditions remains uncertain. Urinary Glc4 was evaluated in 35 genetically confirmed LOPD patients followed for four years with annual functional assessments, spirometry, and quantitative muscle MRI. Glc4 was measured by liquid chromatography-tandem mass spectrometry and normalized to creatinine. Associations with changes in six-minute walk test (6MWT), forced vital capacity (FVC), and thigh fat fraction (FF) were analyzed. Receiver operating characteristic (ROC) analysis assessed the ability of baseline Glc4 to predict clinically meaningful motor decline (>30 m reduction in 6MWT). Multivariate linear regression evaluated whether baseline Glc4 independently predicted 6MWT decline. Glc4 levels were elevated in all patients and showed considerable intraindividual variability. Higher baseline Glc4 was associated with greater functional decline and increased muscle fat replacement. ROC analysis showed good predictive performance (AUC 0.78), with an optimal threshold of approximately 13 mmol/mol creatinine. Baseline Glc4 remained an independent predictor of 6MWT decline in multivariate analysis (p = 0.042). Baseline urinary Glc4 provides relevant prognostic information in LOPD and may serve as a complementary biomarker for routine disease monitoring.PERGAMON-ELSEVIER SCIENCE LTD2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21151NEUROMUSCULAR DISORDERSISSN: 09608966ISSNe: 18732364reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p211512026-06-14T12:41:47Z
dc.title.none.fl_str_mv Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
title Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
spellingShingle Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
Dominguez-González, C
Pompe disease
Glucose tetrasaccharide
Biomarker
Enzymatic replacement therapy
title_short Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
title_full Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
title_fullStr Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
title_full_unstemmed Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
title_sort Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease
dc.creator.none.fl_str_mv Dominguez-González, C
Iannucci, D
Clark, J
Martin-Jiménez, P
Hold, S
Oliva, P
Bischinger, A
Gallardo, E
Diaz-Manera, J
author Dominguez-González, C
author_facet Dominguez-González, C
Iannucci, D
Clark, J
Martin-Jiménez, P
Hold, S
Oliva, P
Bischinger, A
Gallardo, E
Diaz-Manera, J
author_role author
author2 Iannucci, D
Clark, J
Martin-Jiménez, P
Hold, S
Oliva, P
Bischinger, A
Gallardo, E
Diaz-Manera, J
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Pompe disease
Glucose tetrasaccharide
Biomarker
Enzymatic replacement therapy
topic Pompe disease
Glucose tetrasaccharide
Biomarker
Enzymatic replacement therapy
description Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy caused by acid alpha-glucosidase deficiency, leading to glycogen accumulation in skeletal muscle. Reliable biomarkers for monitoring disease progression and treatment response are lacking. Urinary glucose tetrasaccharide (Glc4), a marker of glycogen turnover, is well established in infantile-onset Pompe disease, but its prognostic value in LOPD under longitudinal real-world conditions remains uncertain. Urinary Glc4 was evaluated in 35 genetically confirmed LOPD patients followed for four years with annual functional assessments, spirometry, and quantitative muscle MRI. Glc4 was measured by liquid chromatography-tandem mass spectrometry and normalized to creatinine. Associations with changes in six-minute walk test (6MWT), forced vital capacity (FVC), and thigh fat fraction (FF) were analyzed. Receiver operating characteristic (ROC) analysis assessed the ability of baseline Glc4 to predict clinically meaningful motor decline (>30 m reduction in 6MWT). Multivariate linear regression evaluated whether baseline Glc4 independently predicted 6MWT decline. Glc4 levels were elevated in all patients and showed considerable intraindividual variability. Higher baseline Glc4 was associated with greater functional decline and increased muscle fat replacement. ROC analysis showed good predictive performance (AUC 0.78), with an optimal threshold of approximately 13 mmol/mol creatinine. Baseline Glc4 remained an independent predictor of 6MWT decline in multivariate analysis (p = 0.042). Baseline urinary Glc4 provides relevant prognostic information in LOPD and may serve as a complementary biomarker for routine disease monitoring.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21151
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21151
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv PERGAMON-ELSEVIER SCIENCE LTD
publisher.none.fl_str_mv PERGAMON-ELSEVIER SCIENCE LTD
dc.source.none.fl_str_mv NEUROMUSCULAR DISORDERS
ISSN: 09608966
ISSNe: 18732364
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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