Clinical, biochemical and genetic profiling of X-linked adrenoleukodystrophy in Egyptian pediatric patients: a hospital-based study

Abstract Background X-linked adrenoleukodystrophy, the most common peroxisomal disorder, is caused by ABCD1 gene mutations. This genetic disorder is characterized by the defective degradation of very long-chain fatty acids. This study aimed to assess the frequency, clinical spectrum, and molecular background of X-linked adrenoleukodystrophy among a group of Egyptian pediatric patients with clinical suspicion of peroxisomal disorder. Subjects and methods This study included 120 high-risk Egyptian children presented to Cairo University Children’s Hospital (CUCH) with the clinical suspicion of peroxisomal disorder. X-linked adrenoleukodystrophy diagnosis was confirmed by the very long-chain fatty acids testing using gas chromatography/mass spectrometry followed by sequencing of the ABCD1 gene in patients with abnormal very long-chain fatty acids results. Results 6/120 (5%) patients (from 4 unrelated families) had a high level of very long-chain fatty acids. The cerebral phenotype was the most common presentation, and white matter demyelination was the most common radiological finding. Three ABCD1 gene pathogenic variants (c. 293 C > T (p. Ser98Leu), c. 1511T > C (p. Leu504Pro) and c. 1415₁416del p. (Gln472Argfs*83) ) had been detected in 5 patients and one de novo likely pathogenic variant c. 1511T > C (p. Leu504Pro) had been detected in one patient. Conclusions Epidemiological studies regarding the prevalence and genetic basis of peroxisomal disorders among Egyptian children are currently scarce. In our recent study, we investigated the frequency of these disorders within a group of suspected cases.