A newly published study in the European Journal of Pediatric Neurology shows the Echo Heterogeneity Index (EHI) could be a better ultrasound evaluation approach to monitor the severity of Pompe disease.

Enzyme replacement therapy (ERT) is the current standard of care for Pompe disease. However, many patients on ERT still report muscle involvement. This happens when the muscle fibers have been critically affected or accumulated a lot of glycogens.

Moreover, autophagy dysfunction has also been reported to affect the trafficking of the replacement enzyme, resulting in a lack of response to ERT.


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Ultrasound is a valuable tool in screening the specific patterns of muscle involvement (in association with the disease severity) in Pompe disease, even before the clinical weakness ensues. Heckmatt scale is a semiquantitative 4-point score based on the increased muscle echogenicity and decreased bony bone reflection. This scale has been frequently used in visually grading the sonographic muscle structure.

In this study, the research team adopted shear modulus from the elastography and the EHI, a new index, from the B-mode scan as 2 quantitative ultrasound parameters to assess the muscle texture and motor functions among patients with Pompe disease.

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The study enrolled patients aged 5 or more years with Pompe disease between September 01, 2018, and January 31, 2021, in a single medical center in Taiwan. Patients fulfilling at least 1 of the following criteria were included: GAA enzyme deficiency in white blood cells or skin fibroblasts by enzyme assay or 2 pathogenic variants in trans in the GAA gene detected by gene sequencing.

“In this study, there were three major findings. First, the EH indices obtained from the ImageJ analyses were negatively correlated with the Heckmatt scale grades in each/every muscle,” the authors highlighted. “Second, the relationship between the shear modulus and the Heckmatt scale in different muscle groups was inconsistent. Third, lower EH indices of lower limb muscles are associated with worse motor functions in patients with Pompe disease.”

The authors noted several limitations in their study, including the small sample size, which may limit generalizations of the study findings. Moreover, the study did not enroll a control group which created uncertainty about whether the EH index shows a significant difference between normal and pathological muscles. Additionally, they didn’t conduct muscle magnetic resonance imaging.

“The clinical implication of the study is that the EH index can be adopted as [an ultrasound] evaluation approach to monitor disease severity and assess ERT response,” the authors concluded. “Further studies with larger samples, including pathophysiological correlations regarding shear wave elastography, will be warranted in patients with Pompe disease.”

References

Chiu Y-H, Liao C-L, Chien Y-H, et al. Sonographic evaluations of the skeletal muscles in patients with Pompe disease. Eur J Paediatr Neurol. Published online December 06, 2022. doi:10.1016/j.ejpn.2022.12.002