Evaluation of electrospray-tandem mass spectrometry for the detection of phenylketonuria and other rare disorders.

Since a few years ESI-MS/MS has been employed for the simultaneous detection of a wide range of inborn errors of metabolism. The screening center North at the Hamburg University Medical Center processes 40-50,000 samples per year. To assess current developments in neonatal screening, the Northern German Working Group on Neonatal Screening consisting of health care providers, metabolic centers, and screening laboratories was founded. Based on current literature and experience four categories of diseases were established. The first three categories were recommended for screening under constant scientific evaluation, while glutaric aciduria II, beta-ketothiolase deficiency, short-chain acylCoA dehydrogenase deficiency, and homocystinuria were not included in the screening program. In contrast, general screening for phenylketonuria (PKU) remains undisputed and MS/MS screening reduced false positives by simultaneously detecting phenylalanine and tyrosine. Recently, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4))-sensitive PKU has been discovered. We were able to demonstrate that BH(4) treatment without dietary restrictions may be sufficient for certain BH(4)-responsive PKU patients. In general, MS/MS provides a potential to rapidly screen for a wide variety of rare metabolic disorders but a close cooperation between scientists and metabolic doctors is required to constantly evaluate results in terms of improving the outcome of patients.