Toward Newborn Screening of Cerebrotendinous Xanthomatosis: Results of a Biomarker Research Study Using 32,000 Newborn Dried Blood Spots

Abstract Purpose: Cerebrotendinous xanthomatosis (CTX) is a treatable hereditary disorder caused by the deficiency of sterol 27- hydroxylase, which is encoded by the CYP27A1 gene. Different newborn screening biomarkers for CTX have been described, including 7α,12α-dihydroxy-4-cholesten-3-one ( 7α12αC4 ), 5b-cholestane-3 α, 7α,12α,25-tetrol glucuronide(GlcA-tetrol), GlcA-tetrol to tauro-chenodeoxycholic acid (t-CDCA) ratio (GlcA-tetrol/t-CDCA), and tauro- trihydroxycholestanoic acid (t-THCA) to GlcA-tetrol ratio (t-THCA/GlcA-tetrol ). We set out to evaluate these screening methods in a research study using 32,000–55,000 newborn dried blood spots (DBS). Method: