Background The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (NBS) in eastern coastal areas of China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area. Methods The NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis. Results Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was—IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short‐chain acyl‐CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were—PAH gene for PKU: c.728G > A, c.442‐1G > A, c.611A > G, c.721C > T; PTS gene for non‐classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del. Conclusion This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of China. Implementing NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for NBS to detect IEM.

Background: Clinical expression of DUOX2 gene variants is differential in patients with congenital hypothyroidism (CH). We investigated whether the molecular etiology of DUOX2 gene variants in CH patients can predict disease outcome, drug dosage, and follow-up period. Potential pathogenic variants were detected in 98 CH patients using whole-exome sequencing. Differences in diagnostic indicators and sustained Levothyroxine (L-T4)therapeutic dose between biallelic and monoallelic groups were compared. Results: The variant detection rate was 77.55%, and 149 variants were identified across 9 genes. Variants in the DUOX2 gene were of 50 types and showed the highest detection rate, with a frequency of 74.50% (111/149). Variants of interest were p.R1110Q (17.12%, 19/111) and p.K530* (16.22%, 18/111), where the former had a higher incidence of permanent hypothyroidism (PCH; 75%, 9/12). Patients with variants in the ferric oxidoreductase domain are more likely to develop PCH. Heel blood thyroid stimulating hormone (TSH) levels in the monoallelic group (176.50 [111.68, 272.50] mIU/L) were higher than those of the biallelic group (57.50 [15.30, 112.25] mIU/L; P = 0.001). The L-T4 doses of the monoallelic group at 1 and 3 years of age (36.83 ± 8.23 and 39.18 ± 15.71 µg/day, respectively) were significantly higher than those in the biallelic group (25.87 ± 9.05 and 25.38 ± 9.30 µg/day; P = 0.008 and P = 0.030, respectively). Conclusions: Patients with the p.R1110Q variant are more likely to develop PCH. Relatively high heel blood TSH levels in patients with normal-sized in situ glands harboring monoallelic DUOX2 variant evidenced increased doses and follow-up frequency during treatment.