Adrenoleukodystrophy (ALD)
https://www.nature.com/articles/s41525-025-00497-1
X-linked adrenoleukodystrophy (X-ALD) is a rare genetic condition that affects how the body breaks down very long-chain fatty acids (VLCFAs), leading to a buildup in tissues and potential damage to the brain, adrenal glands, and spinal cord. It is caused by mutations in the ABCD1 gene, located on the X chromosome. This study explored somatic mosaicism, which means that not all cells in the body carry the genetic mutation (some cells are normal while others have the faulty ABCD1 gene). This happens when the mutation arises after the egg is fertilised. Using next-generation sequencing (NGS), researchers identified six male infants who were diagnosed with X-ALD through newborn screening but showed a mix of mutated and non-mutated cells. It was noted that the mosaic pattern is unusual in males, who usually have either all cells affected or none, because they only have one X chromosome. The proportion of affected cells ranged from 66% to 82% in different tissues, indicating the mutation likely occurred early in development. Out of 227 males diagnosed with X-ALD through two major laboratories, about 1.8% had this mosaic form. Interestingly, all six boys with mosaic X-ALD were clinically stable, with no signs of neurological or adrenal problems in early life. This study shows that mosaicism may be more common in X-ALD than previously thought and could explain some of the differences in how severely the disease affects individuals. Including mosaicism information in genetic reports may help improve diagnosis, predict disease outcomes, and guide treatment plans for children identified through newborn screening.