Skeletal Muscle Mass Lower in Children With Fabry Disease

Low skeletal muscle mass may be an early manifestation of fabry disease (FD), according to a new report.

However, the report also found no significant difference between the body mass indexes (BMIs) of children with FD and those without. The report was published in Orphanet Journal of Rare Diseases.

Early symptoms of FD—a rare disease caused by a deficient activity of lysosomal hydrolase α-galactosidase A—include neuropathic limb pain, hypohidrosis, angiokeratoma, corneal opacity, and gastrointestinal discomfort, wrote the study authors.

Previous reports have suggested that children with FD are more likely to be underweight, but it has not been clear whether that was inherent to the disease itself or a consequence of gastrointestinal tract involvement, they said.

The authors decided to investigate whether weight and body composition changes might be an early sign of FD. To find out, they analyzed clinical data from 18 children with FD who sought care at the Children’s Hospital of Zhejiang University School of Medicine between 2014 and 2022.

Most of the children (n = 14) were boys. They had an age range of 6 to 17 years, and they came from 6 Chinese provinces. Thirteen of the children—all boys—had the classical phenotype of FD, while the remaining 5 children had late-onset classes.

The children underwent whole body dual energy X-ray absorptiometry scans (DXA) to assess their body composition. Their whole body muscle mass was calculated by subtracting bone mass from fat-free mass, and appendicular skeletal muscle mass was calculated by adding arm and leg muscle mass.

The investigators found that half of the children had abnormal BMIs (7 of 13 in the classical-phenotype group and 2 of 5 in the late-onset cohort). All but 2 of the children had heights that were normal for their ages, suggesting that the lower BMIs of many of the children were related to being underweight. The authors said the differences they found in BMI among the children with FD compared with reference values of healthy children were not statistically significant.

According to DXA analysis, 3 children, including 2 children with the classical phenotype, had abnormal fat mass indexes. Further, 12 children, 10 of whom had the classical phenotype, had abnormal fat-free mass indexes.

Compared with healthy Chinese controls, 8 classical-phenotype patients (61.5%) had a significant reduction in muscle mass, appendicular skeletal muscle mass, and lower-limb skeletal muscle mass. In late-onset patients, skeletal muscle mass was characterized as “mild low” compared with healthy controls. Taken together, the investigators said it appears low skeletal muscle mass is common in early FD.

The authors said the causes of low skeletal muscle mass in patients with FD require further investigation, but they said it may have to do with direct destruction of muscle fibers and/or abnormal capillary function resulting from the destruction of intramuscular vascular endothelial cells.

They cautioned that their report was based on a small sample size and children from a single country. They said some of the differences reported may be specific to the Chinese or Asian population.

Although it was limited in size, the investigators said their study represents the first attempt to examine body composition and muscle mass in patients with early FD.

“We found that skeletal muscle involvement was common in our pediatric patients, suggesting that low skeletal muscle mass may be one of the early manifestations of FD,” they concluded. “Physicians need to pay close attention to this aspect in children with FD.”

Reference

Lu Z, Huang G, Yu L, et al. Low skeletal muscle mass as an early sign in children with fabry disease. Orphanet J Rare Dis. Published online July 21, 2023. doi:10.1186/s13023-023-02806-2