X-linked adrenoleukodystrophy in women: a cross-sectional cohort study.

[adrenomyeloneuropathy]

X-linked adrenoleukodystrophy is the most common peroxisomal disorder . The disease is caused by mutations in the ABCD 1 gene that encodes the peroxisomal transporter of very long -chain fatty acids . A defect in the ABCD 1 protein results in elevated levels of very long -chain fatty acids in plasma and tissues . The clinical spectrum in males with X-linked adrenoleukodystrophy has been well described and ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination . As in many X-linked diseases , it was assumed that female carriers remain asymptomatic and only a few studies addressed the phenotype of X-linked adrenoleukodystrophy carriers . These studies , however , provided no information on the prevalence of neurological symptoms in the entire population of X-linked adrenoleukodystrophy carriers , since data were acquired in small groups and may be biased towards women with symptoms . Our primary goal was to investigate the symptoms and their frequency in X-linked adrenoleukodystrophy carriers . The secondary goal was to determine if the X-inactivation pattern of the ABCD 1 gene was associated with symptomatic status . We included 46 X-linked adrenoleukodystrophy carriers in a prospective cross-sectional cohort study . Our data show that X-linked adrenoleukodystrophy carriers develop signs and symptoms of myelopathy (29 /46 , 63 %) and /or peripheral neuropathy (26 /46 , 57 %). Especially striking was the occurrence of faecal incontinence (13 /46 , 28 %). The frequency of symptomatic women increased sharply with age (from 18 % in women <40 years to 88 % in women >60 years of age ). Virtually all (44 /45 , 98 %) X-linked adrenoleukodystrophy carriers had increased very long -chain fatty acids in plasma and /or fibroblasts , and /or decreased very long -chain fatty acids beta -oxidation in fibroblasts . We did not find an association between the X-inactivation pattern and symptomatic status . We conclude that X-linked adrenoleukodystrophy carriers develop an adrenomyeloneuropathy -like phenotype and there is a strong association between symptomatic status and age . X-linked adrenoleukodystrophy should be considered in the differential diagnosis in women with chronic myelopathy and /or peripheral neuropathy (especially with early faecal incontinence ). ABCD 1 mutation analysis deserves a place in diagnostic protocols for chronic non-compressive myelopathy .