Introduction: Currently available therapies for X linked adrenoleukodystrophy (XALD) are successful when administrated to asymptomatic or minimally symptomatic patients.  For this reason newborn screening (NBS) has been advocated to offer timely intervention. However, for a condition to be added to the Recommended Uniform Screening Panel (RUSP), one of the key elements is the demonstration of high performance of the screening test in a population-based pilot. In order to assess clinical validity and performance metrics of a high-throughput assay, we are conducting a prospective study of 100,000 anonymized newborn dried blood spots (DBS).

Methods: A two tier approach, analysis of C20- to C26-lysophosphatidylcholines (LPCs) in DBS by Flow Injection Analysis tandem mass spectrometry (FIAMS/MS) and, when abnormal, by Liquid Chromatography (LC-)MS/MS was used. Molecular genetic analysis of the ABCD1 gene was performed on those samples with abnormal MS/MS results.

Results: To date we analyzed 74,460 NBS samples. Following the two-tier approach, ten samples were submitted for ABCD1 testing.  Of these, two were found to be hemizygote males and one a heterozygote female. No testing was performed to exclude other peroxisomal disorders in the remaining seven cases.

Conclusion/Discussion: These preliminary data prove feasibility of NBS for peroxisomal disorders to be feasible. They also confirm the incidence the disease (ca. 1:17,000 males). Upon completion of the study reference and disease ranges will be determined which will guide result interpretation and further improve NBS performance (http://www.clir-r4s.org/).