To describe the prevalence of seizures in boys with childhood cerebral x-linked adrenal leukodystrophy (ccALD) and to determine the relationship of seizure timing and severity to ccALD disease timing, severity, and progression.

X-linked adrenal leukodystrophy is the most common peroxisomal disorder affecting 1 in 7000 boys and can present with adrenal insufficiency, inflammatory leukodystrophy or myeloneuropathy.  Approximately 30% of males present with rapidly progressive childhood cerebral demyelination between 3 and 8 years old (ccALD).  The prevalence of seizures and relationship to ccALD disease progression and severity in this population has not been carefully described. 

Retrospective chart review at two leukodystrophy centers to describe X-ALD severity and the presence of seizures in a cohort of boys <18 years old with ccALD.  

77 boys with ccALD were identified, of whom 23 experienced seizures (30%).  Average length of follow up was 4 years. 87% of those with seizures were diagnosed with X-ALD after symptoms developed and often were diagnosed during the evaluation of their first seizure.  Diffuse slowing was the most common EEG finding; 52% of those with seizures and EEG had epileptiform discharges.  Seizures were more common in patients with higher disease burden (MRI and functional status).  Seizure severity correlated with ccALD disease severity.  Age at onset of cerebral ALD did not correlate with the presence or absence of seizures; first seizure can occur before or after the diagnosis of ccALD.

This is the largest cohort of patients with ccALD with seizures reported to date.  Seizures in ccALD are more common than previously reported. X-ALD should be in the differential diagnosis for boys presenting with first time seizure, including in the absence of overt cognitive or motor deficits.  The presence of peroxisomal dysfunction and ABCD1 mutation is less important in the pathogenesis of seizures than cerebral disease burden.