Low skeletal muscle mass as an early sign in children with fabry disease

Orphanet J Rare Dis. 2023 Jul 21;18(1):199. doi: 10.1186/s13023-023-02806-2.

PMID: 37480128

Zhihong Lu, Guoping Huang, Ling Yu

Highlights: Low skeletal muscle mass is a common early symptom in children with Fabry disease (FD), suggesting that skeletal muscle is significantly affected in the early stages of FD.

Abstract

Background & Aims: Due to a deficiency of lysosomal α-galactosidase A, Fabry disease (FD), a rare X-linked metabolic storage disorder, results in an accumulation of glycosphingolipids in the body. Occasionally, FD patients have been described as being underweight and having a low BMI. Body composition analysis to identify the reason and whether being underweight is typical in the early stages of FD have not been documented.

Methods: From July 2014 through December 2022, children who received a diagnosis of FD at the Children's Hospital of Zhejiang University School of Medicine were enrolled. Medical records were used to acquire clinical data. The International Society of Clinical Densitometry's standard operating procedure was followed to evaluate body composition (fat mass, FM; fat free mass, FFM; and bone mass) using whole-body dual energy X-ray absorptiometry scans (DXA). Fat-free mass minus bone mass was used to compute total body muscle mass. The combined muscle mass of the arms and legs was used to compute appendicular skeletal muscle mass (ASM). The FM, FFM, ULSM and LLSM indices were calculated by dividing the total FM, FFM, and upper and lower limb skeletal muscle mass (ULSM and LLSM) by the height squared.

Results: 18 kids in total, 14 boys and 4 girls, were enrolled. Five kids—one male with the N215S mutation and four girls—had the late-onset phenotype, while thirteen boys had the classical phenotype. Two of the five children with the late-onset phenotype (40%) and seven children with the classical phenotype (53.8%) both had abnormal BMIs. 16 of the 18 kids (88.9%) had heights that were within the normal range, indicating that the main cause of the low BMI was underweight. According to DXA body composition analysis, 12 children (9 boys and 3 girls) had abnormal FFMIs and 3 children (2 boys and 1 girl) had abnormal FMIs. For the classical phenotype, 10 (76.9%) of the 13 kids had abnormal FFMI values, compared to 2 (15.4%) of the kids with abnormal FMI values. When compared to Chinese controls of the same age and sex, eight patients (61.5%) with the classical phenotype had significantly lower muscle mass index, ASM index, and LLSM index values. In comparison to controls, late-onset patients also showed mildly decreased skeletal muscle mass. The findings suggested that early FD is frequently accompanied with low skeletal muscle mass.

Conclusions: This is the first investigation on early Fabry disease patients' body composition and muscle mass. Indicating that skeletal muscle is extensively impaired in the early stages of FD, low skeletal muscle mass is a frequent early symptom in children with Fabry disease.

Keywords: Absorptiometry, Children, Fabry disease, Skeletal muscle