X-linked Adrenoleukodystrophy (ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene which codes for the transporter of very long chain fatty acids. The clinical spectrum in males with ALD ranges from isolated adrenal insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. As ALD is an X-linked disease, women were previously thought to be asymptomatic carriers. More recently it has been recognized that up to 80% of women with ALD experience some degree of myelopathy. These symptoms, while progressive in nature, are thought to a milder form of the myelopathy seen in men with ALD.

We did a systematic survey of X-ALD clinic patients seen from 2013-2018 at Massachusetts General Hospital. An estimate of 15% in retrospective review has myelopathy and concurrent movement disorders. Detailed medical and family history were obtained. Blood samples were collected for X-inactivation studies. Standardized videotaped neurological examination was performed and subsequently reviewed by two different movement disorder specialists. 

Careful evaluation showed a combination of different movements such as cervical dystonia (4), spasmodic adductor dysphonia (3), action and postural tremor (6), bradykinesia (1) and ataxia (8). All patients exhibited gait difficulties and symptoms of myelopathy.

Movement disorders may be a feature of many hereditary neurodegenerative and metabolic disorders especially among women affected by X-linked disorders. In most of these cases, dystonia and tremor usually occur in the setting of a broader clinical phenotype. Interestingly, movement disorders are not known to be associated with the slowly progressive myelopathy in men with ALD. Hence this finding represents a first distinct phenotype in women with ALD. The notion that ALD may be an underdiagnosed cause of movement disorder among women with ALD warrants further investigation.