MRI scans show different muscle damage in different Pompe types
Lower legs more affected in IOPD kids, while thigh muscles more involved in LOPD
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An MRI study found that children with classic infantile-onset Pompe disease show more widespread involvement of the lower leg muscles than young people with the late-onset form, who tend to have greater involvement of the thigh muscles.
A technique called T2water mapping detected abnormalities in muscles where fat replacement had not yet occurred, suggesting it may serve as a sensitive marker of early disease activity and a tool for monitoring disease progression and guiding treatment decisions.
“A more detailed understanding of [type]-specific patterns of muscle involvement may support the development of reliable imaging biomarkers, which could be applied in longitudinal monitoring, training interventions, and clinical trials,” the research team wrote.
The study, “Quantitative Muscle MRI of the Lower Extremities Reveals Different Patterns of Involvement in Classic Infantile and Young Late-Onset Pompe Patients,” was published in the Journal of Inherited Metabolic Disease.
Pompe disease is caused by a deficiency of an enzyme called acid alpha-glucosidase (GAA). Without enough of this enzyme, glycogen, a stored form of sugar, accumulates and progressively damages muscle tissue. There are two main forms of the disease: Inantile-onset Pompe disease (IOPD) appears shortly after birth with generalized muscle weakness and an enlarged heart. Late-onset Pompe disease (LOPD) can appear from early childhood to late adulthood, progresses more slowly, and tends to be less severe. LOPD primarily affects the muscles around the hips and shoulders, as well as the breathing muscles.
Comparing scans
Without treatment, children with IOPD generally don’t live past early childhood. But children with IOPD who receive standard enzyme replacement therapy (ERT) can survive and reach motor milestones such as standing and walking. For those with LOPD, ERT improves muscle strength, muscle function, and breathing, and a reduction in the death rate has also been reported.
Researchers in the Netherlands used quantitative muscle MRI, a specialized scan, to compare the leg muscles of children and young adults with IOPD or LOPD, most of whom had been treated with ERT.
The study involved eight children with IOPD (ages 6.6 to 15), 12 with LOPD (ages 6.8 to 27.3), and 13 healthy individuals who served as controls.
At the time of the MRI, six of the eight IOPD patients could walk, and seven had significant weakness in the dorsiflexors (the muscles that lift the foot upward). All LOPD patients could walk, while none had dorsiflexor weakness. All were receiving ERT, except for two LOPD patients who showed no symptoms at the time of the study.
The researchers first used MRI to measure the fat fraction, the percentage of a muscle that has been replaced by fat, in upper and lower leg muscles.
Five of the eight IOPD patients and seven of the 12 with LOPD had elevated fat fraction (less muscle tissue). In most cases, fat replacement was mild. At the group level, those with IOPD showed significantly higher fat fractions than healthy controls in three thigh muscles: the biceps femoris brevis, gracilis, and sartorius.
Using T2water measurement, in which higher values indicate early muscle changes such as swelling or inflammation that can occur before fat replacement, the researchers found that values per muscle in healthy controls ranged from 25 milliseconds (ms) to 31 ms, whereas both patient groups showed a wider range: 22 ms to 37 ms in IOPD and 21 to 35 ms in LOPD, a sign of muscle disease.
In IOPD, the tibialis posterior (a muscle in the back of the lower leg) showed significantly higher T2water values than controls. In LOPD, T2water values were significantly higher in several thigh muscles, particularly the adductor longus and adductor magnus, compared with both healthy controls and IOPD patients.
When the researchers combined the two measures to identify muscles in which either the fat fraction or T2water was elevated, a clearer picture of the differences between the two groups emerged.
In the thigh, both groups had a similar overall proportion of affected muscles. Yet the adductor muscles (the muscles along the inner thigh) were more commonly affected in LOPD. Lower-leg muscles were more frequently affected in those with IOPD than LOPD (80% vs. 40%). Most notably, the tibialis anterior (the muscle at the front of the lower leg responsible for lifting the foot) was affected in nearly all IOPD patients (86%) versus one-third of LOPD patients (33%).
Across both patient groups, those with more extensive muscle involvement tended to score lower (worse) on the thigh Quick Motor Function Test (QMFT), a standardized assessment.
For foot dorsiflexion (the ability to lift the foot upward), all six IOPD patients who showed tibialis anterior involvement on MRI had dorsiflexor weakness. In contrast, the one IOPD patient without tibialis anterior involvement on MRI did not. Four LOPD patients had mild tibialis anterior involvement on MRI, but none had dorsiflexor weakness of the foot.
“Quantitative MRI combining fat fraction and T2water mapping reveals distinct patterns of muscle involvement in classic infantile and late-onset Pompe disease patients,” the team concluded. “T2water mapping may detect early muscle changes in the absence of fatty infiltration, highlighting its potential as a sensitive marker of early disease activity and a valuable tool for monitoring progression and guiding treatment strategies in Pompe disease.”
