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-OMD) 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-OMD concentration exceeding 500ng/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 88.08ng/mL (SD=27.74ng/mL). Four newborns exhibited an elevated 3-OMD concentration (range, 939-3241ng/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.