Analysis of genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine.

Objectives: To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4).

Methods: One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022.

Objectives: To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022.

Methods: A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry.

Long-term follow-up of children with carbamoyl phosphate synthase 1 deficiency detected in newborn screening.

Objectives: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province.

Methods: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed.

Results: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing.

Association Analysis of Gene Sequencing by NeoSeq Combined with Tandem Mass Spectrum and Four Neonatal Diseases.

Background: NeoSeq is a new method of gene sequencing for newborn screening. The goal is to explore the relationship between gene sequencing by NeoSeq combined with tandem mass spectrum (TMS) and four neonatal diseases.

Methods: A total of 1,989 newborns from August 2010 to December 2021 were enrolled.

Clinical, biochemical characteristics and genotype-phenotype analysis of congenital hypothyroidism diagnosed by newborn screening in China.

Background: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder worldwide. However, the underlying etiology remains unclear in most patients.

Methods: The newborn screening was performed for TSH in dried blood spots.

[A prospective study of genetic screening of 2 060 neonates by high-throughput sequencing].

Objective: To assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases.

Methods: A total of 2 060 neonates born at Ningbo Women and Children's Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis.

A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China.

Background: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies.

Methods: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS.

[Analysis of clinical features, biochemical indices and genetic variants among children with Short/branched-chain acyl-CoA dehydrogenase deficiency detected by neonatal screening].

Objective: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening.

Methods: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis.

Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China.

Methionine adenosyltransferase deficiency (MATD) is a rare metabolic disorder caused by mono- or biallelic mutations that are not yet well understood. Of the 4,065,644 neonates screened between November 2010 and December 2021, 35 individuals have been diagnosed with an estimated incidence of 1: 116,161 by a cutoff value of methionine 82.7 μmol/L and follow-up over 11 years.

Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency.

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a pan-ethnic complicated inborn error of metabolism but the specific mechanism is not fully understood. A total of 169 patients with NICCD who have biallelic pathogenic variants detected by targeted next-generation sequencing were collected. They were divided into the "Newborn-screen Group" and "Clinical diagnosed Group" depending on the newborn screening results.

A case of methylmalonic acidemia and homocysteinemia cblX type with negative tandem mass spectrometry testing.

A child with methylmalonic acidemia and homocysteinemia cblX type presented focal seizures and epileptic spasms in early infancy, but the tandem mass spectrometry tests showed negative results during neonatal screening or acute attack. Despite treated with a variety of antiepileptic drugs, the child died at age of The blood spot sample of the patient was retrospectively tested with ultrahigh performance liquid chromatography-tandem mass spectrometry, and the increased levels of methylmalonic acid and homocysteine were revealed. Whole exome sequencing showed that the proband had a c.

Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates.

Background: Newborn screening (NBS) has been implemented for neonatal inborn disorders using various technology platforms, but false-positive and false-negative results are still common. In addition, target diseases of NBS are limited by suitable biomarkers. Here we sought to assess the feasibility of further improving the screening using next-generation sequencing technology.

Reference Standards for Newborn Screening of Metabolic Disorders by Tandem Mass Spectrometry: A Nationwide Study on Millions of Chinese Neonatal Populations.

The major clinical problem presently confronting the Chinese newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) is the lack of comprehensive reference intervals (RIs) for disease biomarkers. To close this gap, the Chinese National Center for Clinical Laboratories (NCCL) launched a nationwide study to investigate the dynamic pattern of 35 MS/MS NBS biomarkers and establish accurate and robust RIs. Blood spot samples from 4,714,089 Chinese neonates were tested in participating centers/laboratories and used for study analysis.

Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.

To investigate the incidence rate, clinical and gene mutation characteristics of multiple acyl-CoA dehydrogenase deficiency (MADD) in newborns in Zhejiang province. A total of 3 896 789 newborns were screened for MADD using tandem mass spectrometry in Zhejiang Neonatal Screening Center during January 2009 and December 2020. Patients of MADD were confirmed by urine organic acid and electron transferring flavoprotein (or electron transferring flavoprotein dehydrogenase () gene detection.

Application of genetic screening processor in screening neonatal glucose-6-phosphate dehydrogenase deficiency.

To evaluate the performance of genetic screening processor (GSP analyzer) in neonatal screening for glucose-6-phosphate dehydrogenase (G6PD)deficiency. The accuracy and precision of GSP analyzer was evaluated with the control materials from National Center for Clinical Laboratories and the low and high quality G6PD control kit (fluorescence analysis). GSP analyzer and semi-automatic fluorescence immunoanalyzer (1420 analyzer) were simultaneously used to detect 2622 neonatal screening samples and 41 confirmed samples to analyze the correlation and consistency of the test results; 78 floating samples and 78 non-floating samples were detected to compare the result.

Case Report: Expanding the Digenic Variants Involved in Thyroid Hormone Synthesis-10 New Cases of Congenital Hypothyroidism and a Literature Review.

Congenital hypothyroidism (CH) is the most common neonatal metabolic disorder. Although it has been understood to be a monogenic disease, some CH patients are reported to carry two or more variants at different genes. Here, ten permanent congenital hypothyroidism (PCH) patients were retrospectively reviewed, with elevated levels of serum thyroid-stimulating hormone and levothyroxine dependence during follow-up between 2015 and 2019.

Genetic and epigenetic mechanisms in the development of congenital heart diseases.

Congenital heart disease (CHD) is the most common of congenital cardiovascular malformations associated with birth defects, and it results in significant morbidity and mortality worldwide. The classification of CHD is still elusive owing to the complex pathogenesis of CHD. Advances in molecular medicine have revealed the genetic basis of some heart anomalies.

[Expert consensus for the diagnosis and treatment of glutaricacidemia type 1].

Glutaricacidemia type 1(GA1) is an autosomal recessive disease caused by reduced or missing glutaryl-CoA dehydrogenase activity which hamps metabolism of lysine, hydroxylysine and tryptophan. The catabolic products of glutarylcarnitine and glutaric acid are abnormally accumulated in the body, resulting in metabolic disorders which primarily lead to damage to the nervous system. Clinical manifestations of patients include macrocephaly, dystonia, dyskinesia, and developmental retardation.

[Analysis of gene mutations in a family with combined oxidative phosphorylation deficiency 1].

Objective: To analyze the clinical phenotype and genetic characteristics of a family with combined oxidative phosphorylation deficiency 1 (COXPD-1).

Methods: The whole exome sequencing was performed in parents of the proband; and the genetic defects were verified by Sanger sequencing technology in the dried blood spot of the proband, the amniotic fluid sample of the little brother of proband, and the peripheral blood of the parents.

Results: Whole exome sequencing and Sanger validation showed compound heterozygous mutations of gene c.

[Effects of delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots].

Objective: To explore effects of different delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots (DBS), so as to provide evidence for improving accurate and reliable detection by tandem mass spectrometry.

Methods: A total of 1 254 616 newborn DBS samples in Newborn Screening Center of Zhejiang Province were delivered and stored at room temperature (group A, =338 467), delivered by cold-chain logistics system and stored at low temperature (group B, =480 021), or delivered by cold-chain logistics system and stored at low temperature and low humidity (group C, = 436 128), respectively. The concentrations of amino acids and carnitines in DBS were detected by tandem mass spectrometry.

[Screening and clinical analysis of isovaleric acidemia newborn in Zhejiang province].

Objective: To investigate the incidence,clinical,biochemical and genetic characteristics of isovaleric acidemia (IVA) in Zhejiang province.

Methods: Between January 2009 and December 2019, a total of 3 510 004 newborns were screened for IVA using tandem mass spectrometry. Patients of IVA were confirmed by urine organic acid and gene detection.