Newborn screening for adrenoleukodystrophy: International experiences and challenges.

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• X-linked adrenoleukodystrophy (XALD) is the most common leukodystrophy, affecting approximately 1 in 17,000 individuals.
• Newborn screening (NBS) for XALD has been implemented in several countries and states, including New York since 2013, to facilitate early intervention.

Purpose of the Study:

• To review and analyze existing newborn screening (NBS) algorithms, methodologies, and outcomes for X-linked adrenoleukodystrophy (XALD).
• To identify and address common challenges encountered in countries and states with established XALD NBS programs.

Main Methods:

• Systematic review of 14 peer-reviewed reports on NBS for XALD.
• Analysis of detection methods, including mass spectrometry and ABCD1 gene sequencing, used in NBS protocols.

Main Results:

• NBS enables early surveillance of presymptomatic XALD patients, allowing timely treatment for adrenal insufficiency and cerebral demyelination.
• Studies utilized mass spectrometry and ABCD1 gene sequencing for birth detection of XALD.

Conclusions:

• Early detection through NBS offers potential for life-saving interventions in XALD.
• Key challenges include managing variants of unknown significance, screening females, and ethical considerations due to incomplete understanding of XALD's natural history and genotype-phenotype correlations.