Newborn Screening for Adrenoleukodystrophy
A recent study from the University of Minnesota with a five-year follow-up of boys identified through newborn screening suggests that C26:0-LPC levels at screening may predict early disease onset in ALD. In an editorial for JAMA Pediatrics, Dr. Stephan Kemp and Dr. Marc Engelen, discuss the significance of these findings.
Currently, newborn screening identifies cases in the “Grey Zone”—those with borderline elevated C26:0-LPC levels and variants of unknown significance (VUS) in 𝘈𝘉𝘊𝘋1 . This raises concerns about over-identification and unnecessary follow-up. Recent studies indicate a correlation between higher C26:0-LPC levels and early disease manifestations, challenging prior assumptions that VLCFA levels are not linked to disease severity. These findings could lead to improved newborn screening protocols, including adjustments to C26:0-LPC cutoff levels to better identify patients who will truly benefit from early diagnosis and follow-up.
Validating these insights will require larger, long-term studies and international collaboration to refine newborn screening and enhance understanding of 𝘈𝘉𝘊𝘋1 variant pathogenicity.
To support this effort, ALD Connect launched The Grey Zone project, an initiative aimed at improving the classification of 𝘈𝘉𝘊𝘋1 variants of uncertain significance and determining their potential pathogenicity.
Dr. Troy Lund (University of Minnesota) and Dr. Stephan Kemp are ALD Connect Board Members.
Click here to read the Minnesota publication.