OBJECTIVE: To elucidate the epidemiological characteristics and genetic variant profile of Short-chain acyl-CoA dehydrogenase deficiency (SCADD) among newborns from Hainan Province and evaluate its significance within the local neonatal disease screening panel. METHODS: A total of 84 184 newborns born in Hainan Province from February to December 2024 were included. Tandem mass spectrometry (MS/MS) was employed to detect butyrylcarnitine (C4) and propionylcarnitine (C3) levels in dried blood spots. Screening thresholds were set at C4 > 0.43 μ mol/L and C4/C3 ratio > 0.28. Suspected cases underwent confirmatory testing via urinary ethylmalonic acid analysis by gas chromatography-mass spectrometry and whole-exome sequencing for ACADS gene variants. This study was approved by the Medial Ethics Committee of the hospital (Ethics No.: HNWCMC-2024-55). RESULTS: Six SCADD cases (male-to-female ratio = 1:1) were diagnosed, with all carrying compound heterozygous variants at two loci, yielding a prevalence of 7.13 per 100,000 live births. Four known ACADS gene variants were identified, with both c.322G>A and c.625G>A detected at a frequency of 41.7%. Regular follow-up (as of January 2026) revealed that all diagnosed cases have remained asymptomatic with normal growth and development. CONCLUSION The prevalence of SCADD among newborns in Hainan Province is relatively high, with c.322G>A and c.625G>A as the hotspot variants in the region. Given the absence of clinical phenotypes in all screen-detected cases during long-term follow-up, it is recommended to remove this condition from the routine neonatal screening program for this region to reduce unnecessary anxiety and medical cost.
Humans ; Infant, Newborn ; Neonatal Screening/methods* ; Female ; Male ; Lipid Metabolism, Inborn Errors/epidemiology* ; Acyl-CoA Dehydrogenase/genetics* ; China/epidemiology* ; Follow-Up Studies

BACKGROUND AND OBJECTIVE

Transient congenital hypothyroidism (TCH) refers to temporary deficiency of thyroid hormone identified after birth which later recovers to improved thyroxine production. Its prevalence in the Philippines has not been reported in a large-scale study. Its diagnosis remains difficult due to its numerous possible etiologies. Identifying the predictive factors of TCH may aid in earlier diagnosis and decreased risk of overtreatment. This study aimed to determine the predictive factors for TCH in children with congenital hypothyroidism (CH) detected by newborn screening (NBS) in the Philippines from January 2010 to December 2017.

In this multicenter retrospective cohort study involving 15 NBS continuity clinics in the Philippines, medical records were reviewed, and clinical and laboratory factors were compared between children with TCH and those with permanent congenital hypothyroidism (PCH). Of the 2,913 children diagnosed with CH in the Philippines from 2010 to 2017, 1,163 (39.92%) were excluded from the study due to an unrecalled or lost to follow-up status, or a concomitant diagnosis of Down Syndrome.

Among the 1,750 patients included in analysis, 6.97% were diagnosed with TCH, 60.80% were female, mean gestational age at birth was 38 weeks, and mean birth weight was 2,841 grams. Confirmatory thyrotropin (TSH) was lower and confirmatory free thyroxine (FT4) was higher in the TCH group compared to those with PCH (TSH 32.80 vs 86.65 µIU/mL [p < 0.0001]; FT4 9.90 vs 7.37 pmol/L [p 0.001]). The TCH group required lower L-thyroxine doses compared to the PCH group at treatment initiation and at 1, 2, and 3 years of age (initial 6.98 vs 12.08 µg/ kg/day [p < 0.0001]; at 1 year 1.89 vs 4.11 µg/kg/day [p < 0.0001]; at 2 years 1.21 vs 3.72 µg/kg/day [p < 0.0001]; at 3 years 0.83 vs 3.45 µg/kg/day [p < 0.0001]). Among those with TCH, mean serum TSH decreased significantly after treatment with L-thyroxine (32.80 vs. 6.55 µIU/ mL, p 0.0001). Other factors associated with TCH were results of thyroid ultrasonography (p 0.007), gestational age at birth (p 0.02), and maternal history of thyroid illness (p < 0.0001).

Of all the patients with confirmed congenital hypothyroidism via the newborn screening, 6.97% were diagnosed with transient CH. Factors associated with TCH are confirmatory TSH and FT4, L-thyroxine dose requirements, thyroid ultrasound findings, gestational age at birth, and a maternal history of thyroid illness.

OBJECTIVES: To evaluate the clinical value of next-generation sequencing (NGS) in neonatal disease screening, particularly its advantages when combined with tandem mass spectrometry (MS/MS). METHODS: A prospective study was conducted involving blood samples from 1 999 neonates born at the Shenzhen Guangming District People's Hospital, between May and August 2021. All samples were initially screened using MS/MS and fluorescence immunoassay, followed by NGS to detect high-frequency variation sites in 135 related pathogenic genes. Suspected positive variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification in family studies. RESULTS: No confirmed positive cases were found in the MS/MS analysis of the 1 999 neonates. Genetic screening identified 58 positive cases (2.90%), 732 carriers of pathogenic genes (36.62%), and 1 209 negative cases (60.48%). One case of neonatal intrahepatic cholestasis was diagnosed (0.05%, 1/1 999). Fluorescence immunoassay identified 39 cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency (1.95%, 39/1 999), while genetic screening identified 43 cases of G6PD deficiency (2.15%, 43/1 999). The fluorescence immunoassay also detected 6 cases of hyperthyrotropinemia (0.30%, 6/1 999), all of whom carried DUOX2 gene variants. The top ten pathogenic gene carrier rates were G6PD (12.8%), DUOX2 (8.7%), HBB (8.2%), ATP7B (6.6%), GJB2 (5.7%), SLC26A4 (5.6%), PAH (5.6%), ACADSB (4.6%), SLC25A13 (4.2%), and SLC22A5 (4.1%). CONCLUSIONS NGS can serve as an effective complement to MS/MS, significantly improving the detection rate of inherited metabolic disorders in neonates. When combined with family validation, it enables precise diagnosis, particularly demonstrating complementary advantages in screening for monogenic diseases such as G6PD deficiency.
Humans ; Infant, Newborn ; High-Throughput Nucleotide Sequencing/methods* ; Neonatal Screening/methods* ; Tandem Mass Spectrometry ; Prospective Studies ; Female ; Male ; Infant, Newborn, Diseases/diagnosis* ; Genetic Testing

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVES: To develop a quality control indicator system for neonatal screening of inherited metabolic diseases in obstetric settings, so as to provide a standardized tool for quality control in clinical neonatal screening of inherited metabolic diseases. METHODS: From March to May 2024, a literature review combined with expert clinical experience was conducted to develop a preliminary questionnaire on quality control indicators for neonatal screening of inherited metabolic diseases. The final indicator system was established after two rounds of the Delphi method, and the Analytic Hierarchy Process was used to determine indicator weights. RESULTS: Sixteen questionnaires were distributed in each of the two consultation rounds, with a valid response rate of 100% for both. The expert authority coefficients were 0.863 and 0.876, respectively. Kendall's coefficient of concordance for the importance and feasibility of the indicators ranged from 0.091 to 0.125. The final indicator system comprised 3 primary indicators, 8 secondary indicators, and 28 tertiary indicators for neonatal screening of inherited metabolic diseases in obstetric settings. CONCLUSIONS The quality control indicator system developed using the Delphi method demonstrates a strong systematic structure, high clinical adaptability, and strong operability, and can be effectively applied to quality control in neonatal screening of inherited metabolic diseases in obstetric settings.
Humans ; Infant, Newborn ; Neonatal Screening/standards* ; Quality Control ; Metabolism, Inborn Errors/diagnosis* ; Metabolic Diseases/diagnosis* ; Delphi Technique ; Female ; Quality Indicators, Health Care ; Pregnancy

OBJECTIVES: To evaluate the clinical utility and translational potential of a remote jaundice monitoring system for home-based screening of neonatal hyperbilirubinemia. METHODS: A prospective self-controlled study was conducted, enrolling 538 newborns with gestational age ≥35 weeks, birth weight ≥2 000 g, and postnatal age ≤14 days at the Women's Hospital of Nanjing Medical University from March to October 2023. Four screening protocols with different predictive indicators were developed based on the Chinese Neonatal Transcutaneous Hourly Bilirubin Nomogram. The effectiveness of the system was evaluated, and the feasibility of using the remote jaundice monitoring system in actual home settings was analyzed. RESULTS: A total of 538 paired transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) measurements showed a strong correlation (r=0.85, P<0.001), with 95.0% (511/538) of samples within the 95% limits of agreement. Using TcB ≥ the 95th percentile as the predictive indicator, the system achieved 100% sensitivity, 46.2% specificity, and an area under the receiver operating characteristic curve of 0.731 (95%CI: 0.682-0.780). This approach could reduce unnecessary hospital visits by 41.4% (221/538). CONCLUSIONS The system integrates the QBH-801 transcutaneous bilirubinometer, intelligent early warning, and remote guidance services, establishing a closed-loop "hospital-to-home" management model. It demonstrates high safety and feasibility, with significant clinical translational value.
Humans ; Infant, Newborn ; Female ; Male ; Bilirubin/blood* ; Feasibility Studies ; Prospective Studies ; Hyperbilirubinemia, Neonatal/diagnosis* ; Neonatal Screening/methods* ; Jaundice, Neonatal/diagnosis*

OBJECTIVE: To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics. METHODS: A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J). RESULTS: A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c.1024C>A (p.L342M) and ASS1: c.826A>G (p.M276V), c.695C>T (p.P232L) and c.694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.
Humans ; Infant, Newborn ; Tandem Mass Spectrometry/methods* ; Urea Cycle Disorders, Inborn/diagnosis* ; Neonatal Screening/methods* ; Genetic Testing/methods* ; Female ; Retrospective Studies ; Male ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis* ; Mutation ; Carbamoyl-Phosphate Synthase (Ammonia)/genetics* ; Ornithine Carbamoyltransferase/genetics*

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Human ; Infant, Newborn ; Mass Screening ; Neonatal Screening ; Censuses

Infant, Newborn ; Mass Screening ; Neonatal Screening