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

•Newborn screen for AADC deficiency using dried blood spot 3-OMD as a biomarker is feasible.•We successful detected four newborns with 3-OMD elevation, indicating an incidence of AADC deficiency of 1:32,000.•Prematurity tends to have slightly higher 3-OMD levels.

BackgroundThe 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-OMD) in dried blood spots could be integrated into newborn screening program to precisely predict AADC deficiency.MethodsAfter obtaining parental consent, an additional spot was punched from newborn filter paper, eluted, cleaned, and analyzed by tandem mass spectrometry. Newborns with a 3-OMD concentration exceeding 500 ng/mL were referred for confirmatory testing.ResultsFrom 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.ConclusionNewborn screening of AADC deficiency was achieved with a 100% positive-predictive rate. An association for gestational age could be further elucidated.

Graphical abstractWe conducted a successful pilot newborn screening program for aromatic l-amino-acid decarboxylase (AADC) deficiency using dried blood spot 3-O-methyldopa (3-OMD) as a biomarker. We detected four affected newborns, and there were no false-positive cases.Download high-res image (109KB)Download full-size image