Detection of maple syrup urine disease on newborn screening second tier testing for phenylketonuria

ABSTRACT

Newborn screening for phenylketonuria (PKU) in the Philippines uses a bacterial inhibition assay to detect elevations in phenylalanine (PHE). The BIA sensitivity is affected by substances such as antimicrobials. Semiquantitative second-tier screening with thin layer chromatography (TLC) verifies inconclusive PKU screens. Maple syrup urine disease (MSUD) is a prevalent inborn error of metabolism in the Philippines that is currently not part of the Philippine newborn screening program. We report on the incidental detection of MSUD by second-tier TLC PKU screening in order to begin to establish the evidence necessary for its inclusion in the Philippine Newborn Screening Program. We reviewed the PKU newborn screening database from September 1, 1996 to June 12, 2008 to document the number of cases of elevated LEU detected incidental to confirming PHE elevations by second-tier TLC. Elevated LEU findings were studied further to document the number of MSUD cases. From September 1, 1996 to June 12, 2008, 966,096 babies were screened for PKU and 28,248 (2.9%) required second-tier testing. Of these, 403 had elevated PHE and 9 were confirmed to have either classic PKU or hyperphenylalaninemia. Fifty-three of 28,248 babies had normal PHE concentrations but elevated LEU concentrations. These babies were recalled and a second dried blood spot was requested. Of these, 15 had elevated LEU and were subsequently confirmed to have MSUD. Two babies had concurrent elevations of PHE and LEU, but both were deceased at the time of recall. Confirmation of 15 MSUD cases was almost twice as high as the number of PKU/HPA confirmed cases. Since MSUD patients were detected incidental to PKU screening and there was no initial MSUD screening, the incidence of MSUD is almost certainly much greater. The number of MSUD cases incidentally detected confirms that MSUD exists at a significantly higher prevalence in the Philippine newborn population than PKU, and its inclusion in the newborn screening panel should be considered as soon as feasible.