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Objective To study the influence of postnatal age and season of sample collection on congenital hypothyroidism (CH) screening and to determine the appropriate cut-off value. Method From January 2015 to December 2017, neonatal thyroid stimulating hormone (TSH) screening data in Guangzhou were retrospectively analysed. The infants were assigned into four groups according to sampling postnatal age:24～＜48 h, 48～＜72 h, 3～＜7＜d and≥7 d, and assigned into another four groups according to their birth seasons. Based on the data of 2015 and 2016, the cut-off value of TSH for hypothyroidism were adjusted. The data of 2017 were used to verify the accuracy of the adjusted cut-off value. The cut-off value was determined based on the receiver operating characteristic (ROC) curve and percentile method. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of the cut-off value were also calculated. Result A total of 459854 newborns were screened from 2015 to 2016. 7329 were positive in preliminary screening, 371 were still positive after recall for re-examination, and 318 were confirmed with CH eventually. The optimal TSH cut-off value calculated using ROC curve was 9 mIU/L, with a percentage of 98.7. The cut-off value with sampling time≥48 h was set to 9 mIU/L in spring, summer and autumn, and 10 mIU/L in winter. The cut-off of sampling time 24～＜48 h was set to 10 mIU/L in all seasons. The data of 264993 newborns screened in 2017 were verified using the adjusted cut-off value. The overall positive rate was reduced from 1.27％to 1.02％, and the PPV was increased from 6.07％to 7.58％without adding false negative cases. Conclusion Adjusting cut-off values of TSH for CH screening according to postnatal age and season can effectively reduce false positive rates.
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Objective@#To reveal the molecular epidemiologic characteristics of glucose-6-phosphate dehydrogenase (G6PD) gene and to evaluate based on the genetic analysis the newborn screening program performance and enzymatic diagnosis of G6PD deficiency in Guangzhou.@*Methods@#G6PD enzyme activities were measured by quantitative fluorescence assay in dry blood spots of 16 319 newborns(8 725 males, 7 594 females) 3-7 days after birth in Guangzhou Newborn Center. They were born in Guangzhou form Oct. 1 to 20, 2016. The cutoff value of G6PD was less than 2.6 U/g Hb in dry blood spots. G6PD deficiency was diagnosed when G6PD<1 700 U/L or G6PD/6PGD<1 in red blood cells. Genetic analysis of G6PD gene was performed on the dry blood spot samples of 823 newborns (including positive 346, negative 477)with various levels of G6PD enzyme activities through fluorescence PCR melting curve analysis(FMCA) to detect 15 kinds of mutations reported to be common among Chinese.G6PD gene Sanger sequency was performed in seven highly suspicious patients with negative results by FMCA.@*Results@#(1) Using the cutoff value of G6PD< 2.6 U/g Hb , a total of 687(4.2%) newborns showed positive screening results, including 560 (6.4%) males and 127(1.7%) females. (2) Among the newborns with positive screening results, 214 males and 122 females were randomly chosen for G6PD gene analysis. The results showed that 197 (92.1%) males were hemizygote and 108(88.6%) females were mutation carriers with one to four alleles. Among the newborns with negative screening results, 41 males with G6PD 2.6-2.8 U/g Hb and 436 females with G6PD 2.6-4.5 U/g Hb were chosen for genetic analysis.Mutations were detected in 5(12.2%)boys, and 226(51.8%) girls were carriers.G6PD gene Sanger sequency of seven highly suspicious patients showed that c.406C>T, c.551C>T, c.835A>T hemizygote were found in 3 male's samples, respectively. (3) The estimated prevalence of harboring mutation was 6.0% in males and 13.5% in females according to rates of mutation in samples with various levels of G6PD enzyme activities. Six common mutations were c.1388G>A、c.1376G>T, c.95A> G, c.871G>A, c.1024C>T, c.392G>T, accounting for 95.5% of detected alleles .(4) based on results of G6PD gene analysis, the newborn scereening of G6PD deficiency with cutoff value G6PD<2.6 U/g Hb yielded a positive predict value(PPV) of 93.5%, a false-positive rate of 0.5%, and a sensitivity of 99.0% for males. A PPV of 88.5%, a false-positive rate of 0.2% . The prevalence of severe type G6PD deficiency in females was about 1.5%. Compared with to genetic analysis, the sensitivity and PPV of G6PD activity assay in red blood cells were 95.5%, 97.2%, respectively.@*Conclusions@#The prevalence of G6PD deficiency in males was 6.0% in Guangzhou. Six mutations c.1388G>A, c.1376G>T, c.95A>G, c.871G>A, c.1024C>T, c.392G>T accounted for 95.5%. The cutoff value of G6PD<2.6 U/g Hb innewborn screening program and the criteria of biochemical diagnosis could accurately identify G6PD deficiency . Combined with biochemical and molecular analysis will improve the accuracy of diagnosis of G6PD deficiency and detect more heterozygous females.
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Objective@#To explore the TPO, DUOX2 and DUOXA2 genotypes and phenotypes of children with permanent congenital hypothyroidism(PCH) suspected dyshormonogenesis in Guangzhou, identified and treated at Guangzhou Newborn Screening Center. Six of them were born between 2011 and 2012.@*Method@#Retrospectively analyzed the clinical data of 9 children with PCH suspected dyshormonogenesis. Genetic analysis of TPO, DUOX2 and DUOXA2 genes were performed with Sanger sequencing.@*Result@#Of the 9 patients, four were identified variants in TPO gene including three cases with biallelic variants and one case with monoallelic variant. Novel c. 1784G>C( p. R595T) variant in TPO was predicted to be damaging by SIFT and PolyPhen-2. Four patients harbored monoallelic known variants in DUOX2 gene and the other one harbored heterozygous known mutation c. 738C>G(p.Y246X) in DUOXA2 gene.Two adolescent patients with biallelic variants in TPO gene showed classical PCH phenotypes with thyroid goiter or nodules. The six patients with monoallelic variant in TPO, DUOX2 or DUOXA2 presented variable phenotypes. Among the 433 578 newborns in the 2011-2012 cohort, there were 156 cases of CH. Six of these cases were PCH suspected dyshormonogenesis, among which 1 case was confirmed TPO biallelic variants and 5 cases were monoallelic variants of TPO, DUOX2, or DUOXA2 genes.@*Conclusion@#TPO and DUOX2 variants are the common molecular pathogenesis in children with PCH suspected dyshormonogenesis. Monoallelic variants in TPO, DUOX2 or DUOXA2 are associated with PCH and showed wide variability in their phenotypes. The novel variant p. R595T in TPO is probably a pathologic variant. The prevalence of PCH caused by TPO gene defects is rare in Guangzhou.
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Objective To investigate the clinical effects of vitrectomy combined with cataract surgery in the treatment of proliferative diabetic retinopathy (PDR V-VI stage).Methods A total of 80 patients with proliferative diabetic retinopathy from January 2012 to January 2014 were divided into the single group and the combined group according to the surgical method.Patients of the single group were treated by vitrectomy while patients of the combined group were treated by vitrectomy combined with cataract surgery.The incidence of retinal reattachment,postoperative vision and surgical complications between the two groups were compared.Results Compared with the single group,the incidence of retinal reattachment was higher in combined group (P ＜ 0.05).The postoperative vision improvement was better than that in single group,the difference was significant (P ＜ 0.05).And the surgical complications in combined group was less than that in single group,the difference was significant (P ＜ 0.05).Conclusion Vitrectomy combined with cataract surgery in the treatment of proliferative diabetic retinopathy has a better clinical effect which is safe and reliable,and it can improve the rate of retinal reattachment and reduce surgical complications.
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Objective To discuss the effect of neonatal congenital hypothyroidism (CH)screening in preterm infants.Methods The result of 208 713 cases neonatal congenital hypothyroidism screening in Guangzhou neonatal screening center were analyzed,including 11589 cases preterm infant and 197 124 cases of full term.The difference of screening positive rate and incidence between preterm infants and full term infants group were compared and the efficiency of preterm infants congenital hypothyroidism screening were estimated.Results A total of 208 713 newborns were screened and the screening positive rate was 1.39%.123 cases were confirmed positive for CH and the incidence rate was 1 /1 697.124 cases were screening positive in preterm infants and the screening posi-tive rate was 1.06%.14 cases were confirmed positive for CH and the incidence rate was 1 /828 in preterm infants group.2 771 cases were screening positive in full term infants and the screening positive rate was 1.41%.109 cases were confirmed positive for CH and the incidence rate was 1 /1 809 in full term group.The screening positive rate was lower and the incidence rate of preterm infants group(χ2 =4.89,P <0.05)was higher than that of the full term infants group(χ2 =8.26,P <0.05).Conclusion The incidence rate of congenital hypothyroidism is higher in preterm infants.Neonatal screening is an effective measure for early diagnosis of preterm infants congenital hypothyroidism.