Differing clinical presentations of two unrelated cases of X-linked adrenoleukodystrophy with identical mutation Y296C in the ABCD1 gene.

OBJECTIVES: X-linked adrenoleukodystrophy is a genetically determined disorder that causes varying degrees of malfunction of the adrenal cortex and central nervous system. Our aim was to investigate the occurrence of known, or new, mutations in the ABCD1 gene in two unrelated patients with clinical suspicion of the adrenoleukodystrophy.

METHODS: Two unrelated patients - the first with behavioral changes, the second with progressive cognitive deficit - underwent a clinical and genetic examination in order to establish a diagnosis and discover a possible mutation.

RESULTS: In the first patient, a 47 year old man, the clinical examination showed dementia of the frontal type and spastic quadriparesis. The patient also suffered from adrenal insufficiency for 6 years. An MRI showed confluent hyperintensive lesions in FLAIR images in the frontal lobe of both hemispheres. The second patient, a 16 year old boy, suffered also from Addison's disease since the age of 9, and developed cognitive deficit in the course of one year. The MRI showed posterior atrophy and hyperintensive lesions in parietal and occipital lobes in T2WI. In both cases, genetic analyses showed a missense mutation at the codon 887 (A>G) in exon 1 of the ABCD1 gene, predicting the substitution Y296C in the ALD protein.

CONCLUSION: We detected the same mutation of the ABCD1 gene in two unrelated patients with ALD. In the first case there was frontal lobe involvement, in the second case parieto-occipital involvement. Both pathologic involvement and clinical presentation differed in two cases of the same mutation.

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