Molecular Genetics and Metabolism · Jun 17, 2026

Driving treatment for females with X-linked adrenoleukodystrophy

By Zackowski KM, Raymond GV, Fatemi A et al.

OBJECTIVE: To compare adult females with X-linked adrenoleukodystrophy to age-matched controls and to evaluate the influence of this pathology on clinical presentation and responsiveness to exercise. METHODS: 14 females with X-linked adrenoleukodystrophy and 12 age-matched controls participated in a pre-post design with a 12-week exercise intervention. Outcome measures include neurological exam; quantitative strength, sensation, and walking measures; pain and quality of life questionnaires, and 3 T imaging for white matter integrity of brain and cervical spinal cord. RESULTS: At pre-test, females with X-linked adrenoleukodystrophy were significantly worse than controls in hip strength (flexion p = 0.02, extension p = 0.008), sensation (p < 0.0001), walk speed (Timed 25 ft walk p = 0.006, Timed up and go p = 0.02, walk velocity p = 0.13), pain (p = 0.007), and quality of life (p = 0.01). Significant positive changes are found in post-training for strength (flexion p = 0.03, extension p = 0.006) and walking (Timed 25-ft walk p = 0.01, walk velocity p = 0.008). Strength is the most significant factor affecting change in walk velocity in the regression model including group, disability, and imaging. Pain is the only factor that relates to quality of life, however, post training, improved strength moderates this relationship. Age significantly contributes to weakness in X-linked adrenoleukodystrophy but not to vibratory loss. White matter integrity contributes to models of vibratory loss and predicting walking benefits from exercise. INTERPRETATION: This data identifies meaningful outcomes for clinical trials and treatment guidelines for the health of females with X-linked adrenoleukodystrophy. Sensory loss quantification is an important marker of this pathology regardless of age-related changes. Pain significantly impacts quality of life. Importantly, we show that females with X-ALD responded to exercise with improved strength and walking as much as controls, despite starting from a more impaired state.

doi.org/10.1016/j.ymgme.2026.110193PubMed 42341674Interventions