Classic FD phenotype, particularly in males, was associated with reduced exercise capacity, muscle mass and physical performance, supporting the integration of cardiopulmonary exercise testing, physical functional assessments and body composition analysis into the routine evaluation of FD patients.
Key Findings
Results
VO2 peak below 85% of predicted was significantly more frequent in classic phenotype FD patients than in late-onset/VUS patients.
VO2 < 85% of predicted occurred in 53.8% of classic phenotype patients versus 11.5% of late-onset/VUS patients (p < 0.01).
Cardiopulmonary exercise testing (VO2 peak) was used to assess cardiorespiratory fitness.
42 FD patients were enrolled (13 males; mean age 46 ± 13.9 years) across multiple centres.
Patients were stratified by phenotype: classic versus late-onset/Variants of Uncertain Significance (VUS).
Results
Fat-free mass index (FFMI) was significantly lower in classic phenotype patients compared to late-onset/VUS patients.
FFMI was 16.8 ± 1.0 kg/m² in classic phenotype versus 18.6 ± 2.1 kg/m² in late-onset/VUS patients (p = 0.01).
Body composition was assessed via bioelectrical impedance analysis (BIA).
BIA parameters included fat-free mass index (FFMI), fat mass index (FM), and phase angle (PA).
Results
Treated males had significantly lower phase angle (PA) than untreated males, and PA correlated strongly with VO2 peak.
Treated males had a PA of 4.8° ± 1.0° versus 7.6° ± 0.9° in untreated males (p = 0.04).
PA correlated with VO2 peak (r = 0.879; p = 0.01).
Treatment included enzyme replacement therapy (ERT) or chaperone therapy.
Phase angle was measured by bioelectrical impedance analysis and reflects cellular integrity and muscle quality.
Results
Classic phenotype males demonstrated markedly reduced handgrip strength and chair-stand test performance relative to reference values.
74.3% of classic phenotype males scored below the 50th percentile in handgrip strength, with a mean of 26.1 ± 7.8 kg.
60.9% of classic phenotype males performed below predicted values in the 30-s chair-stand test, with a mean of 12.4 ± 4.3 repetitions.
Physical function was evaluated using the 6-min walk test, handgrip strength test, 30-s chair-stand test, and short physical performance battery.
Muscle strength was also assessed using isometric and isokinetic knee strength tests.
Results
Self-reported fatigue scores were significantly higher in classic phenotype patients compared to late-onset/VUS patients and in treated patients compared to untreated patients.
Fatigue scores were higher in classic versus late-onset/VUS patients (p = 0.05).
Fatigue scores were higher in treated patients compared to untreated patients (p = 0.02).
Fatigue was assessed using self-report fatigue questionnaires.
This pattern suggests that treated patients, who likely have more severe disease, experience greater fatigue burden.
Methods
The study enrolled 42 genetically confirmed adult FD patients across multiple centres using a cross-sectional design.
42 FD patients were enrolled: 13 males and 29 females; mean age 46 ± 13.9 years.
All participants had genetically confirmed FD and were aged ≥ 18 years.
Demographic and laboratory data were collected alongside physical fitness and function assessments.
Analyses were stratified by sex, phenotype (classic vs. late-onset/VUS), and treatment status (ERT/chaperone-treated vs. untreated).
Vitturi N, Gugelmo G, Gasperetti A, Duregon F, Dalmonico A, Lenzini L, et al.. (2026). Physical Fitness and Physical Function in Patients With Fabry Disease: A Cross-Sectional Multicentre Study.. Journal of cachexia, sarcopenia and muscle. https://doi.org/10.1002/jcsm.70233