Adrenoleukodystrophy (ALD)
https://www.medrxiv.org/content/10.64898/2026.06.30.26356979v1
X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder caused by changes in the ABCD1 gene, leading to the buildup of very long-chain fatty acids in the body. This can affect the brain and adrenal glands, which produce essential hormones. Newborn screening can identify individuals with ABCD1 variants before symptoms appear, although predicting who will develop disease remains challenging. In this study, researchers examined 201 boys identified through newborn screening across six centres in the United States. They wanted to see whether different ABCD1 variants were associated with adrenal insufficiency (AI), which is when the adrenal glands cannot produce enough hormones, or cerebral ALD (cALD), which causes inflammation and damage in the brain. The variants were classified as disease-causing, likely disease-causing, or variants of uncertain significance (VUS), whose effects on health remain unclear. Overall, 26% of boys developed AI and 8% developed cALD. Rates of adrenal insufficiency were highest among boys with disease-causing variants (54%), compared with likely disease-causing variants (16%) and VUS (11%). Researchers also found that higher levels of C26:0-lysophosphatidylcholine (C26:0-LPC), a blood marker of fatty acid accumulation, were associated with an increased risk of developing AI at an earlier age. These findings suggest that combining genetic testing with blood biomarkers could help doctors better predict disease risk and personalize monitoring. An important note is that boys with uncertain variants can still develop symptoms, which highlights the need for continued follow-up.