Genotypes of neonatal inherited metabolic diseases in Zhejiang Provincefrom 2009 to 2021 / 预防医学

ABSTRACT

Objective@#To investigate the genotypes and prognosis of infants with definitive diagnosis of inherited metabolic diseases during neonatal screening in Zhejiang Province from 2009 to 2021, so as to provide insights into the management of birth defects.@*Methods@#The medical records of infants with definitive diagnosis of inherited metabolic diseases by tandem mass spectrometry during neonatal screening in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The prevalence, genotypes and prognosis of inherited metabolic diseases were analyzed. @*Results@#A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535. There were 400 infants with amino acid metabolic disorders (AAD), 342 infants with fatty acid oxidation metabolic disorders and 296 infants with organic acid metabolic disorders (OAD), with incidence of 1/11 767, 1/13 763 and 1\15 902, respectively. There were 32 types of diseases, including 13 types of AAD, 8 types of FAOD and 11 types of OAD identified, and phenylketonuria and tetrahydrobiopterin deficiency (PKU/BH4D), primary carnitine deficiency (PCD) and methylmalonic academia (MMA) were detected as the most common forms of AAD, FAOD and OAD, with incidence of 1/20 827, 1/24 262 and 1\49 030, respectively. A total of 789 infants received genetic testing (76.01%), and genetic testing was performed among 70.00% of infants with AAD, 83.04% of infants with FAOD and 76.01% of infants with OAD. The c.728G >A (p.R243Q) variant was the most common mutation in infants with PKU (29.17%), c.1400C>G (p.S467C) variant was the most common mutation in infants with PCD (33.46%), c.609G>A (p.W203X) variant was the most common mutation in infants with combined MMA (40.00%), and c.1663G>A (p.A555T) variant was the most common mutation in infants with MMA (17.86%). Among the 997 infants (96.05%) with successful follow-up, 973 infants (93.74%) had normal intelligence and physical developments, and 41 infants died (3.95%), including 9 deaths due to AAD, 15 deaths due to FAOD and 17 deaths due to OAD. @*Conclusions @#The incidence of PKU, PCD and MMA was high among infants with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with c.728G>A (p.R243Q), c.1400C>G (p.S467C) and c.609G>A (p.W203X) variants as common gene mutations, respectively. Most infants with inherited metabolic diseases had a favorable prognosis; however, the mortality of OAD was relatively high.