ABSTRACT With increased survival due to enzyme replacement therapy, children with classic infantile Pompe disease tend to develop a clinical phenotype with pronounced distal muscle weakness, while late‐onset patients typically exhibit proximal muscle weakness. This MRI study aimed to characterize lower limb muscle involvement in classic infantile and young late‐onset Pompe patients compared to healthy controls, and examine its relationship with motor function. Quantitative MRI (3‐point Dixon and multi‐echo spin‐echo at 3T) was used to assess fat fraction (FF) and water T2 (T2 water ) in the leg muscles of eight classic infantile patients (6.6–15.0 years), 12 late‐onset patients (6.8–27.3 years), and 13 healthy controls (6.5–26.9 years). Group comparisons were performed (Kruskal–Wallis, post hoc Dunn), and FF and T2 water values were combined to identify the most frequently affected muscles. MRI findings were correlated with Quick Motor Function Test (QMFT) scores for thigh involvement and Medical Research Council (MRC) scores for foot dorsiflexion strength. MRI showed fat replacement and T2 water abnormalities in numerous muscles in both patient groups. Fat replacement was generally mild (< 20%) but reached 69% in some cases. T2 water values ranged from 21 to 37 ms. Classic infantile patients showed more frequent lower leg involvement (80% vs. 40%), while late‐onset patients had predominant thigh involvement, particularly in the adductors. Extensive thigh involvement correlated with lower QMFT scores. Foot dorsiflexion weakness occurred only in classic infantile patients with tibialis anterior involvement. This data suggests a phenotype‐specific pattern of muscle involvement and demonstrates the value of combining FF and T2 water via quantitative MRI for detection of muscle involvement in Pompe disease.
Dorpel et al. (2026) studied this question.