3-O-methyldopa levels in newborns: Result of newborn screening for aromatic L-amino-acid decarboxylase deficiency

Background: The diagnosis of aromatic L-amino-acid decarboxylase (AADC) deficiency is often delayed because a cerebrospinal fluid analysis is required to detect a neurotransmitter deficiency. We here demonstrated that an elevated concentration of L-dopa metabolite 3-O-methyldopa (3-O-MD) in dried blood spots could be integrated into newborn screening program to precisely predict AADC deficiency. Methods: After obtaining parental consent, an additional spot was punched from newborn filter paper, eluted, cleaned, and analyzed by tandem mass spectrometry. Newborns with a 3-O-MD concentration exceeding 500 ng/mL were referred for confirmatory testing. Results: From September 2013 to December 2015, 127,987 newborns were screened for AADC deficiency. The mean 3-OMD concentration in these newborns was 88.08 ng/mL (SD = 27.74 ng/mL). Four newborns exhibited an elevated 3-OMD concentration (range, 939-3241 ng/mL). All four newborns were confirmed to carry two pathologic DDC mutations, indicating an incidence of AADC deficiency of 1:32,000. During the follow-up period, three patients developed typical symptoms of AADC deficiency. Among 16 newborns with mildly elevated 3-OMD levels, six were heterozygous for the DDC IVS6 + 4A > T mutation. Conclusion: Newborn screening of AADC deficiency was achieved with a 100% positive-predictive rate. An association for gestational age could be further elucidated. (C) 2016 Elsevier Inc. All rights reserved.