To evaluate disease burden among female patients with X-linked adrenoleukodystrophy (ALD).

ALD is a single gene disorder caused by mutations in the ABCD1 gene, leading to a progressive myelopathy in adults. While clinical presentation has been well-studied in males, less information is available on symptom prevalence in females. Previous reports estimate that roughly one half of females develop myelopathy in adulthood. We highlight this as an area of unmet need and aim to add to the literature in the largest cohort of females to date.

We performed a retrospective chart review of all female patients with ALD seen in the Massachusetts General Hospital Leukodystrophy Clinic from September 2010 to September 2021. We extracted data on major neurological signs and symptoms.

We identified 70 female patients with ALD, ranging in age from 28-86 years (median = 49.2 years). Sixty-seven (95.7%) patients had at least one neurological sign or symptom. The most common sign was impaired sensation in the lower extremities in 56 (80.0%) patients, followed by hyperreflexia in 51 (72.9%), sensory ataxia (positive Romberg) in 42 (60.0%), abnormal gait in 38 (54.3%), lower extremity weakness in 32 (45.7%), hypertonia in 19 (27.1%), and impaired coordination in 12 (17.1%) patients. The most common symptoms were bladder dysfunction and pain, both reported in 53 (75.7%) patients. Other common symptoms were gait/walking difficulty in 50 (71.4%), balance difficulty in 40 (57.1%), lower extremity stiffness in 37 (52.9%), bowel dysfunction in 36 (51.4%), numbness in 30 (42.9%), and paresthesia in 29 (41.4%) patients. Twenty-four (34.3%) patients used walking aid for ambulation.

Our results show that most females with ALD develop neurological deficits in adulthood severe enough to have a negative functional impact. Understanding the disease course in females will help define sex-specific differences in ALD and inform the pathophysiology and appropriate treatment for this disorder.