Abstract
Background: Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the mitochondrial branched-chain keto acid dehydrogenase complex. We investigated whether liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a more reliable and accurate method than MS/MS in the diagnosis and management of patients with MSUD in a Chinese population.
Methods: A total of 370 dried blood spots (DBS) from healthy neonates, 44 DBS specimens from phenylketonuria neonates, and 38 DBS samples from 10 MSUD patients were retrospectively tested using the LC-MS/MS method. The results were compared with those obtained by the MS/MS method.
Results: The reference intervals of branched-chain amino acids (BCAAs) and alloiosleucine (Allo-Ile) were estimated for both sexes. In classic MSUD patients, Allo-Ile was markedly elevated (average of 136 μmol/L, which was significantly higher than the normal value, <5 μmol/L). The averages of BCAAs were also markedly elevated continually during the treatment.
Conclusions: The application of the LC-MS/MS method in the measurement of Allo-Ile and BCAAs in DBS is more useful for diagnosing and managing classic MSUD than the MS/MS method.
Conflict of interest statement
Funding: This study was supported by a grant from Shanghai Jiaotong University School of Medicine (12XJ10034) and a grant from the Science & Technology Commission of the Shanghai Municipality Key Program (11dz1950300).
Ethical approval: This study was approved by the Ethics Committee of Xinhua Hospital.
Competing interest: The authors declare no conflicts of interest.
We are grateful to Jiande Zhou and HaoXu for their assistance in obtaining dried blood samples from the newborn screening program. We also thank Jiande Zhou for providing healthy blood for the preparation of the calibrators.
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