Phenotype assignment in symptomatic female carriers of X-linked adrenoleukodystrophy

Approximately 20% of female heterozygotes of X-linked adrenoleukodystrophy (X-ALD) develop neurological symptoms clinically resembling those of adreno myeloneuropathy in men. However, only very few studies have systematically investigated the extent and distribution of nervous and endocrine system in volvement in female carriers of X-ALD. To define the phenotype in symptomat ic female carriers of X-ALD we performed a prospective study including eigh t symptomatic women who were followed for a mean period of 3.4+/-1.8 years (range 1-6) using standardized clinical examination protocols, magnetic res onance imaging and spectroscopy, evoked potential studies including visual, brainstem auditory somatosensory and magnetic evoked potentials, neurograp hic recordings and endocrine studies. Spastic paraparesis and decreased vib ration sense in the lower extremities were the most frequent clinical findi ngs. Slightly hyperintense symmetric parieto-occipital white matter lesions on magnetic resonance imaging were detectable in two of seven cases, and t he N-acetylaspartate/ choline ratios on magnetic resonance spectroscopy wer e decreased in three of seven patients. P40 latencies were abnormal in all patients, and central motor conduction times to the lower extremities in se ven of eight patients. Prolonged latencies of brainstem auditory evoked pot ential waves III-V or interpeak latencies of waves I-III, I-V and III-V wer e detectable in all patients. The degree of walking impairment was positive ly correlated with the duration of clinical disease (r=0.58, P < 0.05) and inversely correlated with the N-acetylaspartate/choline ratios (r=0.85; P < 0.05). Neurographic recordings revealed only subtle abnormalities, suggest ing that nervous system involvement in symptomatic female carriers of X-ALD is confined mainly to the central nervous system. No evidence of adrenal i nsufficiency was detected in any of the patients.