Symptomatic female heterozygotes for adrenoleukodystrophy: A report of two unrelated cases and review of the literature

We report two cases of unrelated female heterozygotes for adrenoleukodystrophy (ALD) who have developed progressive neurological disease. Both presented with a progressive myelopathy in midlife and one has since also developed a peripheral neuropathy. Both women had elevated very long chain fatty acid (VLCFA) levels. One patient has been on Lorenzo's oil for 2 years with normalisation of her plasma VLCFA assays but her condition has progressed relentlessly and the second discontinued Lorenzo's oil after 1 month due to unacceptable weight loss. Review of the literature reveals that significant neurological symptoms develop in 15-20% of female heterozygotes and that abnormalities on neurological examination occur in up to 55%. Despite a not excessively rare estimated gene frequency of 1/20,000 the diagnosis of a symptomatic heterozygote for ALD is rarely made in the absence of an affected male relative with most patients misdiagnosed as suffering from multiple sclerosis.