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Pathogenic variants in the ABCD1 gene cause adrenoleukodystrophy (ALD), a progressive metabolic disorder characterized by three core clinical syndromes: a slowly progressive myeloneuropathy, a rapidly progressive inflammatory leukodystrophy (cerebral ALD), and primary adrenal insufficiency. These syndromes are not present in all individuals, and are not related to genotype. Cerebral ALD and adrenal insufficiency require early detection and intervention and warrant clinical surveillance because of variable penetrance and age of onset. Newborn screening has increased the number of presymptomatic individuals under observation, but clinical surveillance protocols vary.We used a consensus-based modified Delphi approach among 28 international ALD experts to develop best-practice recommendations for diagnosis, clinical surveillance, and treatment of ALD patients. We identified 39 discrete areas of consensus. Regular monitoring to detect the onset of adrenal failure and conversion to cerebral ALD is recommended in all male patients. Hematopoeitic cell transplant (HCT) is the treatment of choice for cerebral ALD. This guideline addresses a clinical need in the ALD community worldwide as the number of overall diagnoses as well as presymptomatic individuals is increasing due to newborn screening and greater availability of next generation sequencing. The poor ability to predict the disease course informs current monitoring intervals but remains subject to change as more data emerges. This knowledge gap should direct future research and illustrates once again that international collaboration amongst physicians, researchers and patients is essential to improving care.

OBJECTIVE/BACKGROUND: X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disease that causes progressive gait and balance problems. Leg discomfort, sleep disturbances, and pain contribute to daily disability. We sought to investigate the prevalence and severity of Restless Legs Syndrome (RLS) in patients with ALD. PATIENTS/METHODS: We administered questionnaires and conducted diagnostic telephone interviews to assess RLS severity. We retrospectively extracted data from neurological examinations, functional gait measures, and laboratory assessments. RESULTS AND CONCLUSIONS: Thirty-two adults with ALD (21 female, 11 male) were recruited to participate. Thirteen patients (40.6%) had RLS (10/21 females and 3/11 males). The median age of RLS onset was 35 years [IQR = 22 – 54]. Patients with RLS had more signs and symptoms related to myelopathy, but not the brain demyelination seen in ALD. This pilot study suggests a high prevalence of RLS in adults with ALD, which may contribute to sleep problems and impair quality of life.