Multi-omics approach for screening of X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a single-gene disorder that predominantly affects the cerebral white matter, peripheral nerves, adrenal cortex, and testis. As the most prevalent genetic disorder within the peroxisomal group, X-ALD is characterized by impaired metabolism of very long-chain fatty acids (VLCFAs) resulting from mutations in the ABCD1 gene, located on the Xq28 chromosome. The clinical presentation varies widely, with neurological manifestations ranging from progressive, fatal, inflammatory cerebral leukodystrophy in young boys to non-inflammatory axonal myelopathy and peripheral neuropathy in adult males. Over 70% of affected males experience primary adrenal insufficiency, with females presenting with gonadal dysfunction/primary ovarian insufficiency, loss of hair, and early balding. Molecular evaluation and mutation detection provide the most definitive diagnosis, allowing for the assessment of genetic risk and carrier status. This study aims to investigate the mutational spectrum and biochemical prognosis of X-ALD, providing insights into its pathophysiology and implications for clinical management.