Sex-specific newborn screening for X-linked adrenoleukodystrophy

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• X-linked adrenoleukodystrophy (ALD) poses significant health risks to males, including adrenal insufficiency and cerebral leukodystrophy.
• Elevated very long-chain fatty acids (VLCFA), specifically C26:0-lysophosphatidylcholine (C26:0-LPC), are biomarkers for ALD.
• Newborn screening allows for early detection and intervention, crucial for preventing irreversible damage in affected males.

Purpose of the Study:

• To evaluate the feasibility and effectiveness of a sex-specific newborn screening program for X-linked adrenoleukodystrophy (ALD) in the Netherlands.
• To identify males with ALD using a targeted screening algorithm based on C26:0-LPC levels and genetic markers.
• To assess the impact of covariates like gestational age and birth weight on C26:0-LPC concentrations.

Main Methods:

• Implementation of the SCAN (Screening for ALD in the Netherlands) study, a pilot sex-specific newborn screening program.
• Analysis of dried bloodspots from 71,208 newborns for elevated C26:0-LPC levels.
• Confirmation of ALD diagnosis in identified males through genetic testing for ABCD1 variants and clinical evaluation.

Main Results:

• The SCAN study successfully identified four boys with X-linked adrenoleukodystrophy (ALD) among 71,208 screened newborns.
• The sex-specific screening algorithm proved feasible, accurately identifying males with ALD without detecting untreatable conditions in females.
• Covariates such as gestational age, sex, birth weight, and age at blood sampling showed minimal effect on C26:0-LPC concentrations.

Conclusions:

• A sex-specific newborn screening program for X-linked adrenoleukodystrophy (ALD) is feasible and effective in identifying affected males.
• This targeted approach avoids identifying untreatable conditions in females, addressing ethical considerations for countries hesitant to screen girls.
• Early detection through newborn screening facilitates timely management and follow-up for boys with ALD, potentially preventing severe health outcomes.