Molecular characterization of X-linked adrenoleukodystrophy in a Tunisian family: identification of a novel missense mutation in the ABCD1 gene.

Background: X-linked adrenoleukodystrophy (X-ALD) is a recessive neurodegenerative disorder that affects the brain's white matter and is associated with adrenal insufficiency. It is characterized by an abnormal function of the peroxisomes, which leads to an accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues, especially in the cortex of the adrenal glands and the white matter of the central nervous system, causing demyelinating disease and adrenocortical insufficiency (Addison's disease). X-ALD is caused by a mutation in the ABCD1 gene (ATP-binding cassette, subfamily D, member 1), which encodes the adrenoleukodystrophy protein involved in the transport of fatty acids into the peroxisome for degradation.

Objective: We report here a disease-related variant in the ABCD1 gene in a 19-year-old Tunisian boy with childhood cerebral adrenoleukodystrophy.

Methods: The diagnosis was based on clinical symptoms, high levels of VLCFA in plasma, typical MRI pattern and molecular analysis.

Results: Molecular analysis by direct sequencing of the ABCD1 gene showed the presence of a novel missense mutation c.284C>A (p.Ala95Asp) occurring in the transmembrane domain in the proband, his mother and his sister.

Conclusion: Using bioinformatic tools we suggest that this novel variant may have deleterious effects on adrenoleukodystrophy protein structure and function.