Newborn screening of maple syrup urine disease and the effect of early diagnosis

Maple syrup urine disease (MSUD) is a rare disease for which newborn screening (NBS) is feasible but not universally applied in China. We shared our experiences with MSUD NBS. Tandem mass spectrometry-based NBS for MSUD was implemented in January 2003, and diagnostic methods included urine organic acid analysis via gas chromatography–mass spectrometry and genetic analysis. Six MSUD patients were identified from 1.3 million newborns, yielding an incidence of 1:219,472, in Shanghai, China. The areas under the curve (AUCs) of total leucine (Xle), Xle/phenylalanine ratio, and Xle/alanine ratio were all 1.000. Some amino acid and acylcarnitine concentrations were markedly low in MSUD patients. 47 MSUD patients identified here and in other centers were investigated, which included 14 patients identified by NBS and 33 patients diagnosed clinically. Forty-four patients were subclassified into classic (n = 29), intermediate (n = 11) and intermittent (n = 4) subtypes. Due to earlier diagnosis and treatment, screened classic patients showed a higher survival rate (62.5%, 5/8) than clinically diagnosed classic patients (5.2%, 1/19). Overall, 56.8% (25/44) of MSUD patients and 77.8% (21/27) of classic patients carried variants in the BCKDHB gene. Among 61 identified genetic variants, 16 novel variants were identified. MSUD NBS in Shanghai, China, enabled earlier detection and increased survivorship in the screened population.