ATAD3A gene variations in a family with Harel-Yoon syndrome / 浙江大学学报·医学版

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.

Effects of delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots / 浙江大学学报·医学版

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, @*RESULTS@#The concentrations of amino acids and carnitines in the three groups were skewed, and the differences in amino acid and carnitine concentrations among groups were statistically significant (all @*CONCLUSIONS@#Cold-chain logistics system and storage in low temperature and low humidity can effectively reduce degradation of some amino acids and carnitines in DBS, improve the accuracy and reliability of detection, and thus ensures the quality of screening for neonatal metabolic diseases.

Screening and clinical analysis of isovaleric acidemia newborn in Zhejiang province / 浙江大学学报·医学版

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 @*RESULTS@#A total of 15 patients with IVA were diagnosed, with an incidence of 1/234 000. Three patients had acute neonatal IVA, and the rest were asymptomatic. The isovalerylcarnitine (C5) levels were increased in all patients. Twelve children underwent urinary organic acid analysis, of which 11 cases had elevated isovalerylglycine levels, 4 cases with 3-hydroxyisovalerate increased simultaneously. Eleven IVA patients underwent genetic testing, 9 patients were compound heterozygous variants in @*CONCLUSIONS@#The clinical manifestations of IVA are non-specific, and the gene spectrum is scattered. Newborn patients screened by tandem mass spectrometry can receive early diagnosis and treatment, so as to correct metabolic defects and pathophysiological changes.

Application of Region 4 Stork system in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency by tandem mass spectrometry / 中华检验医学杂志

Objective:To investigate the application feasibility of Region 4 Stork (R4S) system, an international collaborative newborn screening data platform, combined with cut-off value analysis in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency (VLCADD) by tandem mass spectrometry (MS/MS).Methods:The retrospective study was performed in 2, 040 072 neonates screened by MS/MS in Neonatal Screening Center of Zhejiang Province, China from October 2013 to July 2018. Nine hundred and ten cases were determined and identified as suspected positive VLCADD neonates by traditional cut-off method of tandem mass spectrometry. The original data of these 910 screened neonates were further analyzed by R4S system. Based on clinical diagnosis and ACADL gene test results, the screening efficiency between two methods was statistically compared.Results:The data of 910 suspected VLCADD-positive cases interpreted by cut-off method were further analyzed by R4S system, and the positive interpretation was reduced to 238 cases (including 9 confirmed positive cases). A total of 16 different mutations were found in ACADL gene sequencing among the confirmed children. The screening false positive rate (FPR) declined from 0.44‰ (901/2 040 072) to 0.11‰ (229/2 040 072), the rate of positive predictive value (PPV) increased from 0.99% (9/910) to 3.78% (9/238), and the specificity increased from 99.96% (2 039 162/2 040 063) to 99.99% (2 039 834/2 040 063). There was a statistically significant difference between cut-off method alone and cut-off method combined R4S system analysis (χ2=393.5, P<0.05). Conclusions:The R4S system combined with cut-off method applied in VLCADD neonatal screening by MS/MS can effectively improve screening performance, reduce false positive rate, and has certain value in clinical application.

Preliminary application of Region 4 Stork project used in newborn screening by tandem mass spectrometry / 中华检验医学杂志

Objective To investigate the feasibility of Region 4 Stork(R4S)project used for newborn screening by tandem mass spectrometry in China.Methods This retrospective study was performed among 362 822 neonates screened by tandem mass spectrometry from May 2015 to April 2016 in Zhejiang newborn screening center.Infants were grouped by screening result category: 83 true positive cases,360 554 true negative cases and 2 185 false positive cases.Raw data was uploaded into R4S website to perform postanalytical interpretive tools, then results were analyzed with interpretation rules.The comparisons of normal population percentiles were done at five selected percentiles between Zhejiang newborn screening center and R4S project with min-max normalization.Results Compared with cutoff system by using R4S project with interpretation rules,the positive predictive value increased from 3.7%to 8.3%,the specificity increased from 99.40%to 99.75%, and the false positive rate declined from 0.6% to 0.2%. The two cases of true positive hyperprolinemia were reported negative, and one case of β-ketothiolase deficiency was misdiagnosis.Totally 311 638 cases in true negative group were resolved by postanalytical interpretive tools,and the remaining 48 916 cases were excluded with interpretation rules.False positive cases were reduced to 897 cases.Results of percentiles comparison showed that levels of some markers were significantly different between zhejiang newborn screening center and R 4S project.Conclusions R4S project effectively improved the newborn screening performance, whereas leaded to a small number of misdiagnosis and missed diagnosis.Besides,many true negative cases should be excluded with interpretation rules.Optimization should be achieved based on local normal population.(Chin J Lab Med,2018,41:300-304)

Antioxidative effect of Tripterygium wilfordii polyglycosides on diabetic rats / 中国药理学与毒理学杂志

OBJECTIVE ToinvestigatethepossibleprotectiveeffectofTripterygiumwilfordiipolyg-lycoside (TWP ) on experi mental diabetic nephropathy (D N ) rats and its possible mechanis m. METHODS Thediabeticmodelwasinducedbyasingleintraperitonealinjectionofstreptozotocin (STZ)65 mg·kg -1 .Three weeks after modeling,TWP 4.5,9.0 and 1 8.0 mg·kg -1 was ig given to rats,once daily,for 8 consecutive weeks.During the experiment,the changes of body mass,hair, mental health of rats were observed.Two days before the end of the experi ment,the rats were placed into metabolic cages to collect 24 h urine in order to detect 24 h urinary albu min excretion rate (UAER). The rats were given TWP for 8 weeks and anesthetized with 1 0%chloral hydrate.The blood was collect-ed fro m the heart and centrifuged,seru m creatinine and urine creatinine were measured,and creatinine clearance (Clcr)was calculated.Blood urea nitrogen (BUN)and the serum catalase (CAT)activity were tested by optical method while the level of seru m superoxide oxygen anion(O2÷)was tested by col-orimetry.The level of malondialdehyde(MDA)was determined by thiobarbituric acid condensation,and glutathione peroxidase (GSH-Px)activity was tested by colorimetry.The right kidney was HE stained to observepathologicalchanges.RESULTS Comparedwithnormalcontrolgroup,theratsinmodel control group developed polydipsia,polyuria,polyphagia,body mass loss,unresponsiveness,brown hair,pale tail and apathy clammy.Besides,blood glucose,BUN and 24 h UAER were significantly higher (P<0.01 ),but Clcr was lower (P<0.01 ).The activity of serum CAT and GSH-Px in renal tissue was significantly lower(P<0.01 ),while the level of serum O2÷ and MDA in the renal tissue was significantly higher(P<0.01 ).Compared with model control group,TWP 9.0 and 18.0 mg·kg -1 could improve the general condition of rats.BUN and 24 h UAER were obviously reduced(P<0.01 ),Clcr and serum CAT were increased obviously(P<0.01 ),the level of MDA and O2÷ were reduced obviously(P<0.01 ),and GSH-Px level was increased(P<0.01 ).TWP 9.0 and 18.0 mg·kg -1 could significantly im-prove the renal histopathological changes of rats.TWP 4.5 mg·kg -1 had no significant effect on the aboveindicators.CONCLUSION TWPhasprotectiveeffectontherenalfunctionofexperimentalDN rats.The mechanis m may be related to inhibition of the oxidative stress and enhance ment of the body antioxidant capacity.