Abstract Neonatal disease screening is a major tool for prevention of birth defects, and monitoring and evaluation of neonatal disease screening facilitates the improvements in screening quality and efficiency. A strict quality control of screening, diagnosis, treatment and follow-up of neonatal diseases is performed in Zhejiang Provincial Center for Quality Control of Neonatal Disease Screening. In this study, the data pertaining to screening of neonatal inherited metabolic diseases, hearing loss and congenital heart diseases were collected in Zhejiang Province from 2018 to 2020, and the screening rate, recall rate of suspected screening-positive neonates, and detection rate of diseases were calculated to assess the quality of neonatal disease screening. The screening rate and recall rate of neonatal inherited metabolic diseases, hearing loss and congenital heart diseases were high in Zhejiang Province, and the detection of screened diseases was stable, indicating a high overall quality of neonatal disease screening. Increasing the impact of neonatal disease screening and consolidating the screening achievements should be given a high priority during the future quality control of neonatal disease screening in Zhejiang Province.

ObjectiveTo explore the screening and therapeutic efficacy of primary carnitine deficiency (PCD) in newborns and mothers.Methods164245 newborns and suspected mothers were investigated for PCD by tandem mass spectrometry (MS/MS).The overall epidemiology,prognosis,and follow-up of the screening program were investigated.ResultsTotally 55 suspected cases were identified at the primary screening stage.Four newborns and three mothers were confirmed as cases of PCD.The incidence rate of newborns was 1 ∶ 40076.All the patients showed normal growth and development during the follow-up.Blood free carnitine level was raised in all three mothers after treatment.ConclusionsScreening for PCD with MS/MS in newborns may represent a valuable procedure in preventive medicine by enabling early diagnosis and treatment before the onset of symptoms.This protocol is also highly efficient and applicable in diagnosis of mothers with PCD.

Abstract Transport of filter paper-dried blood spot samples is a critical procedure during the screening of neonatal inherited metabolic diseases, which is of great significance for the screening accuracy. In order to ensure the timing and safety of sample transport, the cold chain positioning system was initiated by Zhejiang Provincial Center for Quality Control of Neonatal Disease Screening since March 2015. Based on the framework of neonatal disease screening information management system, the function of the logistics transport management system was included in this positioning system, with aims to achieve the monitoring and tracking of sample transport processes through real-time positioning of the sample transport box via China Unicom 4G logistics card and global positioning system/BeiDou Navigation Satellite System. The samples are maintained in a transport environment at 2 to 8 °C via the temperature-controlled box made of 5 °C phase-changed cold-stored materials and general packet radio service (GPRS) temperature recorders. The mean pretest turnover duration reduced from 8.44 days to 5.03 days following introduction of the cold chain positioning system, and the percentage of timely sample delivery increased from 31.69% to 77.90%, while the withdrawal rate of unqualified samples reduced from 0.12% to 0.08%. The cold chain positioning system meets the requirements of transport of filter paper-dried blood spot samples, which has a high potential in screening of neonatal inherited metabolic diseases.

The serum TSH levels of 107 infants with subclinical hypothyroidism (SH) were > 20 mIU/L after 1-8 check-up, along with FT4, TT4, within low normal range. After given small dosage L-T4, for 4 weeks, blood TSH level obviously descended while FT4, TT4, ascended (all P <0.01). Seven cases of thyroid hypogenesis and 7 strumas were found by ultrasonography. It seems appropriate to use dosage of 3-4 μg·kg·-1·d-1 L-T4 in treating SH.

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.

Objective: To evaluate the quality of tandem mass spectrometry (MSMS) screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021. Methods: The data pertaining to MSMS screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The percentage of MSMS screening, percentage of recall of suspected screening-positive infants and incidence of neonatal inherited metabolic diseases were analyzed retrospectively to evaluate the quality of MSMS screening for inherited metabolic diseases. Results: A total of 4 706 916 newborns were screened among 8 297 039 live births by MSMS in Zhejiang Province from 2009 to 2021, and the percentage of MSMS screening increased from 5.48% to 97.54%, with a mean percentage of 56.73%. Of 46 838 suspected screening-positive infants, 45 527 infants were recalled, and the percentage of recall increased from 94.57% to 98.62%, with a mean percentage of 97.20%. 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, and the incidence rates of amino acid metabolic disorder, fatty acid oxidation metabolic disorder and organic acid metabolic disorder were 1/11 767, 1/13 763 and 1\15 902, respectively. Of the 11 cities in Zhejiang Province, the highest percentage of tandem mass spectrometry screening for inherited metabolic diseases was found in Hangzhou City (83.01%), and the highest percentage of recall of suspected screening-positive infants was se en in Zhoushan City (99.08%). Conclusions A high percentage of MSMS screening for neonatal inherited metabolic diseases was observed in Zhejiang Province from 2009 to 2021; however, there was a region-specific percentage of screening, and the recall of suspected screening-positive infants remains to be improved.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Death, Sudden ; etiology ; Hereditary Central Nervous System Demyelinating Diseases ; diagnosis ; etiology ; Humans ; Hydroxymethylglutaryl-CoA Synthase ; deficiency ; Infant, Newborn ; Male ; Mutation ; Oxo-Acid-Lyases ; genetics ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Objective: To investigate the prevalence of galactosemia(GAL), and the characteristics of genotype and phenotype of newborns who were confirmed with GAL in newborn screening in Zhejiang province. Method: The number of all live births, newborn screened infants and all clinical data of confirmed newborns with GAL from October 2013 to March 2015 were retrospectively analyzed by reviewing the data of Zhejiang Province screening center database. And the characteristics of genes and the clinical data of GAL cases who were confirmed by correlative gene test and enzyme activity measurement were analyzed. Result: The prevalence of GAL in Zhejiang province was 1/189 857. Among them, there was 1 case confirmed with GAL typeⅠ (prevalence, 1/759 428), with mutations of c. 904+ 1G>T and c. 687G>A, the enzyme activity of galactose-1-phosphate uridyltransferase (GALT) was 56.4% of controls. And there was 1 case of GAL typeⅡ(prevalence, 1/759 428), with mutations of c. 85G>T and c. 502G>A. There were 2 cases confirmed with GAL type Ⅲ(prevalence, 1/379 714), with mutations of c. 505C>T, c. 452G>A, c. 280G>A and c. 925G>A, the enzyme activity of UDP-galactose-4′-epimerase (GALE) were 42% and 38% of controls, respectively. All cases had different abnormal biochemical marks of liver function, and 1 case had combined hyperlactacidemia or hyperammonemia or increase of multiple kinds of amino acids, respectively. The newborn of GAL type Ⅱ had phacoscotasmus before treatment. All the cases were fed with lactose free milk powder, and all the abnormal parameters were improved during following up. Conclusion The disease of GAL is rare in Zhejiang province, and its genotype distribution is scattered with comparatively mind clinical manifestations, and the cases with early treatment with lactose free milk powder have good prognosis. All cases needed to be treated and followed up for a life-long time. It is recommended that the high risk cases with GAL should be screened as soon as possible.

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: The child was subjected to next generation sequencing (NGS). Candidate variant was analyzed with bioinformatic software. RESULTS: NGS revealed that the child has carried a de novo heterozygous c.4035G>C (p.Gln1345His) variant of the ARID1B gene. The variant was unreported previously and may cause instability of the protein structure. CONCLUSION The de novo missense variant of ARID1B gene may underlie the mental retardation in the child. Above result has enabled genetic counseling and prenatal diagnosis for her family.

OBJECTIVETo delineate the clinical, biochemical and genetic mutational characteristics of a child with mitochondrial complex III deficiency.

METHODSClinical information and results of auxiliary examination of the patient were analyzed. Next-generation sequencing of the mitochondrial genome and related nuclear genes was carried out. Suspected mutation was confirmed in both parents with Sanger sequencing. Heterozygous deletion was mapped with chromosomal microarray analysis and confirmed with real-time PCR.

RESULTSThe patient presented with vomiting, polypnea, fever, metabolic acidosis, hyperlactatemia, hypoglycemia, dysfunction of coagulation and immune system, in addition with increased lactate dehydrogenase and creatine kinase isoenzyme. Elevation of blood alanine and acylcarnitines as well as urinary ketotic dicarboxylic acid were also noted. The patient also presented development delay, mental retardation and hypotonia. Sequence analysis revealed two mutations in the nuclear gene UQCRB, which included a previously reported frameshift mutation c.306_309delAAAA(p.Arg105Lysfs*22) and a novel large deletion encompassing the entire UQCRB gene.

CONCLUSIONThe clinical, biochemical and gene mutation characteristics of a child with mitochondrial complex III deficiency caused by mutations of the UQCRB gene have been delineated.

Adult ; Base Sequence ; Carrier Proteins ; genetics ; Electron Transport Complex III ; deficiency ; genetics ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases ; genetics ; Molecular Sequence Data ; Mutation