Low muscle mass may be early sign of Fabry disease in children

Data from 18 children analyzed to see if underweight is common in early stages

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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An illustration shows the bands of a muscle in cross-section.

Most children with Fabry disease, particularly those with the severe, classic form, have lower than normal skeletal muscle mass that affects the lower limbs more than the upper limbs, a study in China shows.

Skeletal muscles are responsible for voluntary movements and play a vital role in everyday activities.

“This is the first study to examine body composition and muscle mass in early FD [Fabry disease] patients,” wrote the researchers, who said the results suggest “low skeletal muscle mass may be one of the early manifestations of FD.”

“Physicians need to pay close attention to this aspect in children with FD,” the researchers wrote in “Low skeletal muscle mass as an early sign in children with fabry disease,” which was published in the Orphanet Journal of Rare Diseases.

Fabry disease is caused by mutations in the GLA gene, which provides instructions for producing the alpha-galactosidase A (Gal A) enzyme that’s responsible for breaking down fatty molecules, like globotriaosylceramide, into building blocks cells can use. GLA mutations result in these fatty molecules accumulating in small blood vessels and body tissues, causing damage.

Early disease symptoms include limb pain, diminished sweating, skin lesions caused by damaged small blood vessels, and vision and gastrointestinal problems.

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Is underweight common in early Fabry disease?

“Underweight and low body mass index (BMI) [a ratio of height and weight] have been occasionally reported in FD patients, which was thought to mainly be related to gastrointestinal tract involvement,” wrote researchers in China who analyzed data from 18 children (14 boys, four girls) diagnosed with Fabry disease at a children’s hospital in Hangzhou between July 2014 and December 2022 to see if being underweight is common in the early stages of the disease. The children ranged in age from 6 to 16.

All but one boy had classic Fabry disease, a severe form of the disease in which GalA is unable to function or has very low activity. The other boy and the four girls had the milder late-onset form of the disease, wherein GalA has residual activity. None had received specific Fabry treatment such as enzyme replacement therapy.

Two children (11.1%) were short for their age and nine (50%) were underweight, with all but one belonging to the classic disease group (61.5%).

Seven children with the classic disease (53.8%) and two with the late-onset disease (40%) had lower than normal BMI, which was most likely explained by low weight.

Whole-body dual-energy X-ray absorptiometry analyzed the physical condition and the body composition, including fat mass, fat-free mass, and bone mass. Whole muscle mass was calculated as fat-free mass minus bone mass.

Measuring skeletal muscle mass

The skeletal muscle mass in both arms and legs was also measured, including the upper limb and lower limb skeletal muscle mass. Associated indexes were calculated by dividing each measure by the height squared.

The fat mass index (FMI) was low in fewer than five children and the fat-free mass index was abnormal in 12 children (nine boys, three girls).

Compared with the normal values in Chinese children and adolescents aged 6-17, eight children with classic Fabry (61.5%) had a significantly lower muscle mass index, appendicular skeletal muscle index — both arms and legs — and limb skeletal muscle mass index.

“Late-onset patients also had mild low skeletal muscle mass compared to controls,” the researchers wrote, adding that this suggested that late-onset disease has a “less effect on skeletal muscle.”

When comparing average values of the group of children with Fabry with reference values of healthy children, the researchers found Fabry patients had a significantly lower fat-free mass index, muscle mass index, appendicular skeletal muscle index, upper limb skeletal muscle mass index, and lower limb skeletal muscle index. Only BMI and fat mass index weren’t significantly different between children with and without Fabry disease.

The appendicular skeletal muscle index was significantly associated with a patient’s age, body weight, BMI, and levels of creatinine, a product of muscle metabolism, an analysis showed.

“Overall, the data revealed that underweight due partly to low skeletal muscle mass, particularly in the lower extremities, was a common early symptom in Fabry patients,” the researchers wrote, adding the effect was more prominent in children with classic Fabry.

The Fabry-associated reduction of muscle mass might be due to the direct destruction of muscle fibers and/or blood vessels in the muscles, caused by the abnormal deposition of fatty molecules, the researchers said, noting “reduction in muscle mass may also be involved in the development of osteoporosis in FD patients, since there is solid evidence that low muscle mass is associated with a reduction in bone parameters during growth and increases the risk of osteoporosis in adulthood.” In this study, four boys with classic Fabry had lower than normal bone mass.

More research with larger sample sizes is needed, said the researchers, who noted the small number of patients and that they all were from China, which might prevent the findings from being generalized, were limitations of their study.