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

[x-linked adrenoleukodystrophy]

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 ABCD 1 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 .We report here a disease-related variant in the ABCD 1 gene in a 19 -year -old Tunisian boy with childhood cerebral adrenoleukodystrophy .The diagnosis was based on clinical symptoms , high levels of VLCFA in plasma , typical MRI pattern and molecular analysis .Molecular analysis by direct sequencing of the ABCD 1 gene showed the presence of a novel missense mutation c .284 C >A (p .Ala 95 A sp ) occurring in the transmembrane domain in the proband , his mother and his sister .Using bioinformatic tools we suggest that this novel variant may have deleterious effects on adrenoleukodystrophy protein structure and function .