Screening results of 223 368 cases of neonatal genetic metabolic diseases in Zibo by tandem mass spectrometry

Objective To analyze the results of tandem mass spectrometry (MS/MS) screening of 223 368 neonates with inherited metabolic diseases (IMD) in Zibo.

Methods A total of 223 368 cases of dry blood filter paper were collected from Zibo Maternal and Child Health Care Hospital of Shandong Province for IMD screening, and heel blood was collected at 3 to 7 days after birth for IMD screening by MS/MS method. The positive rate of newborn IMD screening in Zibo was analyzed; the incidence types and gene detection results of neonatal IMD in Zibo were analyzed; the follow-up results of IMD neonates in Zibo were recorded.

Results A total of 75 neonates were diagnosed as IMD, with an incidence of 0.034% (75/223 368). Among them, 51 cases of organic acid disorder (OAD) accounted for the highest proportion (0.023%), followed by 13 cases of amino acid disorder (AAD) (0.006%) and 11 cases of fatty acid oxidation disorders (FAOD) (0.005%). Methylmalonic acidemia (MMA) and medium chain acyl coenzyme A dehydrogenase deficiency (MCADD) were the most common IMDs in neonates. In OAD, MMA was the main component. In AAD, hypermethioninemia and Hitlin protein deficiency (NICCD) were the main symptoms. In FAOD, MCADD and primary carnitine absorption disorder (PCD) were the main cases. During the follow-up, 42 cases (56.00%) were normal, 31 cases (41.33%) were stunted, and 2 cases (2.67%) died. Of the 45 MMA newborns, 42 underwent genetic testing. A total of 22 MMACHC gene mutation sites were detected in 40 cases, mainly c.609G >A (29.11%), c.658_ 660delAAG (15.19%), c.482G>A (12.66%), c.80A>G (8.86%). A total of 4 mutational sites of MUT gene were detected in 2 cases. Of the 30 newborns with other types of IMD, 27 underwent genetic testing. A total of 8 ACADM gene mutation sites were detected in 6 cases of MCADD, mainly c.387+1delG (29.11%), c.449_452 del CTGA (15.19%), and c.1076C>T (12.66%); a total of 5 SLC25A13 gene mutation sites were detected in 4 NICCD, mainly IVS16ins3kb (28.57%) and c.852_855 del (28.57%). All developmental delays were OAD, including 30 cases of MMA and 1 case of propionic acidemia.

Conclusion The incidence rate of neonatal IMD in Zibo area is 0.034%, most of neonates suffer OAD, among which the incidence rate of MMA is the highest, and MMACHC gene mutation is the main mutation.