Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy caused by acid α-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 intra-individual 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.
Domínguez-González et al. (Tue,) studied this question.