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, Volume 48 Issue 4 Previous Issue    Next Issue
Advances in newborn screening and immune system reconstitution of severe combined immunodeficiency
HUANG Shumin,ZHAO Zhengyan
J Zhejiang Univ (Med Sci), 2019, 48(4): 351-357.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.01
Abstract( 666 )   HTML( 57 )     PDF(913KB)( 413 )

Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.

Progress on evaluation, diagnosis and management of disorders of sex development
CHEN Guangjie,WANG Xiaohao,TANG Daxing
J Zhejiang Univ (Med Sci), 2019, 48(4): 358-366.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.02
Abstract( 571 )   HTML( 15 )     PDF(928KB)( 284 )

Disorders of sex development (DSD) refer to a group of diseases characterized by abnormal congenital development of chromosomes, gonad or genitals with different pathophysiological changes and clinical manifestations. DSD is more common in neonates and adolescents, and neonates often show genital abnormalities while adolescents show abnormal sexual development during puberty. It is the international consensus that the scope of DSD should include basic clinical evaluation (internal and external genitalia and endocrine hormones), diagnostic confirmation (chromosome, genetic diagnosis), psychological assessment for children and family, treatment (sex assignment, hormone replacement and surgical intervention), potential fertility protection and long-term follow-up, which require the expertise of pediatric endocrinology, pediatric urology, clinical psychology, genetic disciplines, medical images and other related disciplines; that is, individualized management of children with DSD requires an experienced multidisciplinary team (MDT). This article reviews the recent progress on the evaluation, diagnosis and management of disorders of sex development.

Genetic analysis and prenatal diagnosis of a sporadic family with neurofibromatosis type 1
LIU Bei,YANG Yanmei,YAN Kai,CHEN Min,WANG Liya,HUANG Yingzhi,QIAN Yeqing,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 367-372.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.03
Abstract( 668 )   HTML( 17 )     PDF(1079KB)( 216 )

Objective: To identify pathogenic mutation for a family with neurofibromatosis type 1(NF1) and provide prenatal diagnosis for them. Methods: Mutation analysis of the sporadic family with NF1 was performed with target captured next generation sequencing and Sanger sequencing. RNA samples were extracted from the lymphocytes of NF1 patient and her parents. RT-PCR and Sanger sequencing were performed to analyze the relative mRNA expression in the samples. Prenatal diagnosis of the pathogenic mutation was offered to the fetus. Results: A novel splicing mutation c.1260+4A>T in the NF1 gene was found in the proband of the family, but was not found in her parents.cDNA sequencing showed that 13 bases inserted into the 3' end of exon 11 in the NF1 gene lead to a frameshift mutation. Prenatal diagnosis suggested that the fetus did not carried the mutant. Conclusion: The NF1: c.1260+4A>T mutation found in the NF1 patient is considered to be pathogenic, which provides information for family genetic counseling and prenatal diagnosis.

Genetic study of a family of neuronal ceroid lipofuscinosis caused by a heterozygous mutation of CLN6 gene
LOU Tie,HUANG Yingzhi,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 373-377.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.04
Abstract( 540 )   HTML( 8 )     PDF(988KB)( 186 )

Objective: To analyze the genetic cause of a family with autosomal recessive neuronal ceroid lipofuscinoses (NCL). Methods: The proband was screened for mutations within the coding region of the candidate genes through high-throughput targeted sequencing. Potential causative mutations were verified by PCR and Sanger sequencing in the proband and his parents. RT-PCR and TA clone sequencing were performed to investigate whether the mRNAs were abnormally spliced. Results: The sequencing results revealed compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T, which were respectively inherited from his parents. RT-PCR and TA cloning sequencing suggested that the mRNAs were abnormally spliced in two forms due to both mutations. Conclusions: The compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T are possibly the genetic causes of the NCL family. Detection of the novel mutation has extended mutation spectrum of CLN6.

Genetic analysis of a family of Van der Woude syndrome
XU Yuqing,QIAN Yeqing,YAO Weimiao,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 378-383.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.05
Abstract( 548 )   HTML( 7 )     PDF(1034KB)( 187 )

Objective: To analyze clinical and genetic features of a family affected with Van der Woude syndrome. Methods: The umbilical cord blood of the proband and the peripheral blood of the parents were used for the whole exon sequencing to find the candidate gene.Peripheral blood of 9 members of the family were collected for Sanger sequencing verification, bioinformatics analysis and genotype-phenotype correlation analysis. Results: The proband was diagnosed with cleft lip and palate by ultrasound. His father and grandmother had hollow lower lip and all other family members did not have the similar phenotype. A missense c.263A>G (p.N88S) mutation was found in exon 4 of IRF6 gene in the proband, his father and his grandmother.The mutation was not found in other family members. Conclusion: A missense c.263A>G (p.N88S) mutation in IRF6 gene probably underlies the pathogenesis of Van der Woude syndrome in the family and the mutation has been firstly discovered in China.

Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families
YE Qing,ZHANG Yingying,WANG Jingjing,MAO Jianhua
J Zhejiang Univ (Med Sci), 2019, 48(4): 384-389.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.06
Abstract( 490 )   HTML( 8 )     PDF(1021KB)( 167 )

Objective: To investigate genetic characteristics of Alport syndrome. Methods: High-throughput sequencing-based whole exome sequencing was performed in two patients with recurrent unexplained abnormal urinalysis. The pathogenicity of the genetic variations, type of Mendelian genetics, and clinical phenotypes were analysed, and the disease-cause mutations were confirmed in the family members using Sanger sequencing. Results: Two heterozygous splice site mutations of COL4A5 gene c.2147-2A > T (IVS27) and c.646-2A > G (IVS11) (NM_033380) were found in patients of the two families, which showed a co-segregation association with the affected members of the families. Conclusion: Alport syndrome is mainly inherited from direct female patients, and prenatal genetic screening based on amniotic fluid testing can effectively prevent birth defects in patients with a family history of this characteristic phenotype.

Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine
WU Dingwen,LU Bin,YANG Jianbin,YANG Rulai,HUANG Xinwen,TONG Fan,ZHENG Jing,ZHAO Zhengyan
J Zhejiang Univ (Med Sci), 2019, 48(4): 390-396.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.07
Abstract( 716 )   HTML( 20 )     PDF(977KB)( 233 )

Objective: To investigate the genetic characterization of 3-hydroxyisovalerylcarnitine (C5-OH) metabolic abnormality in neonates. Methods: Fifty two newborns with increased C5-OH, C5-OH/C3 and C5-OH/C8 detected by tandem mass spectrometry during neonatal screening were enrolled in the study. Genomic DNA was extracted from the whole blood samples of 52 cases and their parents. Seventy-nine genes associated with genetic and metabolic diseases including MCCC1, MCCC2 were targeted by liquid capture technique. Variation information of these genes was examined by high-throughput sequencing and bioinformatic analysis, and then was classified based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The genetic types were classified as wild-type, MCCC1-maternal-mutation, MCCC1-paternal-mutation and MCCC2-mutation. Wilcoxon rank-sum test was performed for the increased multiples of C5-OH calculated in neonatal screening. Results: Twenty one MCCC1 variants (14 novel) were identified in 37 cases, 6 MCCC2 variants (5 novel) in 4 cases. The increased multiple of C5-OH calculated in MCCC1-maternal-mutation and MCCC2-mutation groups were significantly higher than that in wild-type group (all P < 0.05), while there was no significant difference between MCCC1-paternal-mutation group and wild-type group (P>0.05). Conclusion: Mutations on MCCC1 and MCCC2 genes are the major genetic causes for the increased C5-OH in neonates, and maternal single heterozygous mutation can contribute to the moderately to severely increased C5-OH.

Genetic analysis of a fetus with multiple malformations caused by complex translocations of four chromosomes
LUO Yuqin,SHEN Min,SUN Yixi,QIAN Yeqing,WANG Liya,YU Jialing,HU Junjie,JIN Fan,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 397-402.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.08
Abstract( 655 )   HTML( 11 )     PDF(996KB)( 236 )

Objective: To conduct genetic analysis in a fetus with complex translocation of four chromosomes. Methods: G-banded chromosome karyotype analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed in a fetus with multiple malformations. Peripheral blood chromosome karyotype and FISH were also carried out for the parents. Results: The fetal amniotic fluid karyotype was 46, XY, t(12; 13)(q22; q32). SNP array analysis showed that there were 20 192 kb duplication at 1q42.13q44 and 13 293 kb deletion at 15q26.1q26.3 in the fetus. The results of karyotype and SNP array were inconsistent. FISH analyses on the parental peripheral blood samples demonstrated that the mother was a cryptic 46, XX, t(1; 15)(q42.1; q26.1) translocation. The fetus had inherited 46, XY, t(12; 13)(q22; q32) from his father and der(15)t(1; 15)(q42.1; q26.1) from his mother. Conclusions: The 1q42.13q44 duplication and 15q26.1q26.3 deletion may have contributed to the abnormal sonographic features of the fetus. The combination of cytogenetic, SNP array and FISH techniques was beneficial for providing an accurate genetic counseling.

Noninvasive prenatal screening for twin pregnancy: an analysis of 2057 cases
YIN Yixuan,ZHU Hui,QIAN Yeqing,JIN Jinglei,MEI Jin,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 403-408.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.09
Abstract( 542 )   HTML( 7 )     PDF(905KB)( 258 )

Objective: To analyze the results of noninvasive prenatal screening (NIPS) for fetal chromosome aneuploidy in twin pregnancy. Methods: A total of 2057 women with twin-pregnancy between 12-26+6 weeks were recruited from Women's Hospital, Zhejiang University School of Medicine, Hangzhou Municipal Women's Hospital and Jiaxing Maternal and Child Health Hospital during February 2015 to August 2018. The cell-free DNA was extracted from the peripheral blood sample for DNA library, and non-invasive prenatal testing (NIPT) was performed by high-throughput sequencing technique. The fetal karyotype analysis or neonatal karyotype analysis was performed in pregnant women with fetal chromosome aneuploidy, and all subjects were followed up. The efficiency of NIPS testing for twin aneuploidy was calculated. Results: NIPS revealed chromosome abnormalities in 11 out of 2057 twin pregnant women, 9 cases were confirmed chromosome abnormalities, 2 cases were normal and no false negative cases. In this screening, the detection rate, sensitivity, specificity, positive predictive value, false positive rate of NIPS were 100.00%, 100.00%, 99.90%, 81.82%, 0.10%. Those were 100.00%, 100.00%, 99.95%, 87.50% and 0.05% for trisomy 21, 100.00%, 100.00%, 100.00%, 100.00%, 0.00% for trisomy18, and the specificity and false positive rate for trisomy13 were 99.95% and 0.05%, respectively. Conclusion: NIPS can detect fetal chromosomal aneuploidy rapidly and accurately in twin pregnancies, and it is of value in clinical application.

Association of maternal age with fetal sex chromosome aneuploidies
LEI Yu,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 409-413.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.10
Abstract( 500 )   HTML( 7 )     PDF(897KB)( 207 )

Objective: To analyze the impact of maternal age on sex chromosome aneuploidies (SCA). Methods: Pregnant women who had karyotype analysis of amniotic fluid in Women's Hospital, Zhejiang University School of Medicine from January 2014 to July 2018 were recruited. The association of the maternal age with fetal SCAs was analyzed. Results: The incidence of 45, X in age group >34- < 38 was lower than that of ≤ 28 age group (P < 0.05). For the incidences of total sex chromosome trisomy and 47, XXY in age groups 34- < 38 and ≥38 were higher than age groups ≤28 and >28-34 (P < 0.05 or P < 0.01). The incidence of 47, XXX in age group ≥ 38 was higher than that in age group>28-34 (P < 0.05). However, the incidence of 47, XYY had no differences among the four groups (P>0.05). After excluding the high risk of sex chromosome abnormalities by non-invasive prenatal testing (NIPT), we found that for 45, X, the incidences of two groups with advanced age were lower than that of ≤ 28 year-old group of age group (P < 0.05 or P < 0.01), and incidence in age group >34- < 38 was also lower than that in age group >28-34 (P < 0.05). The other results were consistent with those without excluding the high risk of sex chromosome abnormalities by NIPT. Conclusion: Advanced age decreases the incidence of 45, X, but increases the risk of sex chromosome trisomy, especially 47, XXX and 47, XXY.

Single nucleotide polymorphism microarray in prenatal diagnosis of fetuses with absent nasal bone
YU Jialing,SUN Yixi,HU Junjie,QIAN Yeqing,LUO Yuqin,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 414-419.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.11
Abstract( 373 )   HTML( 8 )     PDF(905KB)( 181 )

Objective: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in prenatal genetic diagnosis for fetuses with absent nasal bone. Methods: Seventy four fetuses with absent nasal bone detected by prenatal ultrasound scanning were recruited from Women's Hospital, Zhejiang University School of Medicine during June 2015 and October 2018. The chromosome karyotypes analysis and SNP array were performed. The correlation between absent fetal nasal bone and chromosome copy number variants was analyzed. Results: Among 74 fetuses, 19 were detected to have chromosomal abnormalities, including 16 cases of trisomy-21, 1 case of trisomy-18 and two cases of micro-deletion/duplication. Among 46 cases with isolated absence of nasal bone, 3 had trisomy-21, and 1 had a micro-duplication. Absence of nasal bone in association with nuchal translucency thickening had a higher rate of abnormal karyotypes compared with isolated absence of nasal bone (χ2=32.27, P < 0.01). Conclusion: Fetuses with absent nasal bone and nuchal translucency thickening are likely to have chromosome abnormalities, and SNP array testing is recommended to exclude the chromosome abnormalities.

Application of single nucleotide polymorphism microarray in clinical diagnosis of intellectual disability or retardation
HU Junjie,QIAN Yeqing,SUN Yixi,YU Jialing,LUO Yuqin,DONG Minyue
J Zhejiang Univ (Med Sci), 2019, 48(4): 420-428.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.12
Abstract( 508 )   HTML( 7 )     PDF(967KB)( 156 )

Objective: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in patients with intellectual disability/developmental delay(ID/DD). Methods: SNP array was performed to detect genome-wide DNA copy number variants (CNVs) for 145 patients with ID/DD in Women's Hospital, Zhejiang University School of Medicine from January 2013 to June 2018. The CNVs were analyzed by CHAS software and related databases. Results: Among 145 patients, pathogenic chromosomal abnormalities were detected in 32 cases, including 26 cases of pathogenic CNVs and 6 cases of likely pathogenic CNVs. Meanwhile, 18 cases of uncertain clinical significance and 14 cases of likely benign were identified, no significant abnormalities were found in 81 cases (including benign). Conclusion: SNP array is effective for detecting chromosomal abnormalities in patients with ID/DD with high efficiency and resolution.

Prenatal diagnosis and pregnancy outcomes of 22q11.2 duplication syndrome: analysis of 8 cases
MEI Jin,LIU Jiao,WANG Min,ZHANG Wen,WANG Hao,LU Sha,HE Chaying,JIN Chunlei
J Zhejiang Univ (Med Sci), 2019, 48(4): 429-433.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.13
Abstract( 763 )   HTML( 10 )     PDF(899KB)( 214 )

Objective: To investigate the relationship between 22q11.2 duplication and clinical phenotype. Methods: Eight fetuses with 22q11.2 duplication syndrome diagnosed by chromosome microarray analysis (CMA) through amniocentesis from February 2015 to March 2017 were enrolled in the study. The prenatal diagnostic indications, fetal ultrasound, chromosome karyotype, peripheral blood CMA results of parents, pregnancy outcomes and follow-up of postnatal growth and development were retrospectively analyzed. Results: Prenatal serological screening indicated 6 cases with high risk of trisomy 21, 1 case with nuchal fold (NF) thickening and 1 case of maternal chromosomal balanced translocation. Fetal ultrasonography showed 1 case of NF thickening, 1 case of fetal cerebral ventriculomegaly and 6 cases with normal ultrasound. CMA demonstrated that the size of duplication was between 651 kb and 3.26 Mb, and 22q11.2 duplication. Parents' CMA results revealed that 6 cases inherited from one of the parents with normal phenotype, and the parents of 2 cases refused the CMA test. Two couples chose induced labor; 6 cases of continued pregnancy had normal phenotypes at birth. All 6 cases were followed up with longest of 3.5 years. The growth and psychological development were normal in 5 cases, and one case was growth retardation. Conclusion: There were no specific clinical phenotypes in 22q11.2 duplication syndrome, and most of them were inherited from one parent who has normal phenotype.

Prognosis of fetuses with cystichygroma and nuchal translucency/nuchal fold thickening on prenatal echography
WANG Yayun,CHEN Yuan,YANG Mengmeng,XI Fangfang,ZHAN Qitao,JIANG Ying,ZHAO Baihui,LUO Qiong
J Zhejiang Univ (Med Sci), 2019, 48(4): 434-438.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.14
Abstract( 447 )   HTML( 10 )     PDF(897KB)( 263 )

Objective: To analyze the prognosis of fetuses with cystic hygroma (CH) or nuchal translucency (NT) or nuchal fold (NF) thickening detected by prenatal echography. Methods: From January 2014 to December 2015, 124 fetuses with CH and NT/NF thickening on prenatal echography were enrolled from Women's Hospital of Zhejiang University School of Medicine. The basic clinical information, ultrasonic results, pregnancy outcomes and newborn follow-ups were analyzed. The cases were grouped by prognosis and the factors affecting prognosis were analyzed with logistic regression. Results: There were 85 cases of labor induction including one stillbirth and 39 cases delivered. Except one infant who died after birth, all live births survived with good prognosis. Univariate analysis showed that the gestational age at diagnosis of poor prognosis group was earlier than that of good prognosis group (P < 0.01); and the former group also had higher hydrops fetalis rate and additional structural anomalies rate (all P < 0.01). Multivariate regression analysis showed that hydrops fetalis (OR=90.105, P < 0.05) and additional structural anomalies (OR=61.854, P < 0.05) were risk factors of poor prognosis in fetuses with CH and NT/NF thickening. Conclusions: Fetuses with diagnosed CH or NT/NF thickening on prenatal ultrasonography are likely to be associated with chromosomal abnormality. Early gestational weeks, hydrops fetalis and additional structural anomalies may indicate poor prognosis.

Prenatal diagnosis and management of fetal hepatic hemangioma
ZHANG Dandan,WANG Junmei
J Zhejiang Univ (Med Sci), 2019, 48(4): 439-445.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.15
Abstract( 552 )   HTML( 8 )     PDF(1023KB)( 309 )

Objective: To review the application of medical imaging in diagnosis and management of fetal hepatic hemangioma. Methods: Clinical data and imaging findings of 14 cases of fetal hepatic hemangioma, who were diagnosed prenatally and followed up in Women's Hospital of Zhejiang University School of Medicine from February 2014 to September 2018 were retrospective reviewed. Results: The fetal hepatic hemangiomas were single lesions in all 14 cases, and most of them were located in the right lobe of the liver (13/14). Ultrasound images were mainly hypoechoic with heterogeneity, the honeycomb-like or grid-like anechoic regions were presented in 9 lesions and circumferential blood flow was observed with low to moderate blood flow resistance index. MRI findings showed well-defined lesions with low signal intensity on T1WI, and high or slightly high signal intensity on T2WI. Among 14 cases, there were 8 cases of induced labor and 6 cases of continuing pregnancy. In 6 cases of successful delivery, 2 were treated with propranolol, 4 cases were followed-up without treatment. The growth and development of 6 children were normal. The lesions of hepatic hemangioma showed no significant changes in 3 children and were reduced in the other 3 children, of whom the lesion was complete disappeared in 1 case. Conclusions: Fetal hepatic hemangiomas present relatively typical imaging characteristics, and prenatal diagnosis can be made with ultrasound and MRI. If there are no complications, the fetus with hepatic hemangioma can be delivered at full term with a good outcome.

Ultrasound diagnosis of left inferior vena cava and double inferior vena cava in fetus
ZHANG Ziwei,WANG Junmei
J Zhejiang Univ (Med Sci), 2019, 48(4): 446-452.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.16
Abstract( 1242 )   HTML( 6 )     PDF(1061KB)( 335 )

Objective: To evaluate the application of ultrasonography in prenatal diagnosis of left inferior vena cava and double inferior vena cava in fetus. Methods: The clinical data and ultrasonographic findings of the fetuses with left inferior vena cava (18 cases) or double inferior vena cava (16 cases) were retrospectively analyzed. Results: The ultrasonographic images of left inferior vena cava showed that in the transverse view of the fetal upper abdomen the inferior vena cava and abdominal aorta were in the normal position; below the level of the hilum, the inferior vena cava was located behind the left side of the abdominal aorta; at the level of the hilum, it crossed the front of the abdominal aorta and run diagonally to the upper right, forming the right inferior vena cava and finally entered into the right atrium. The ultrasonographic images of double inferior vena cava showed that in the transverse view of the fetal lower abdomen, in front of spine there were three transections of blood vessels; in coronal plane of abdomen, the veins run on both sides of the abdominal aorta and entered to the iliac vein of the same side. In 34 cases of abnormal inferior vena cava, there were 17 cases complicated with other system abnormalities, including 13 cases of cardiac anomalies. Conclusions: The left inferior vena cava and double inferior vena cava have characteristic imaging findings, and prenatal diagnosis can be made with ultrasonography. This type of congenital deformity is frequently complicated with other system abnormalities, which should be excluded in fetus, especially for heart system.

Assessment of fetal superior mesenteric artery and vein by three-dimensional power Doppler sonography
TANG Xianpeng,TAO Ruoling,ZHANG Xinghao,JIN Qiuzi,HE Wei
J Zhejiang Univ (Med Sci), 2019, 48(4): 453-458.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.17
Abstract( 477 )   HTML( 4 )     PDF(1044KB)( 145 )

Objective: To analyze the application of three-dimensional power Doppler sonography (3-DPDS) in evaluation of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) in second-trimester fetus. Methods: Three-dimensional volume probe was used to collect the 3-DPDS blood flow images in 50 normal fetuses of 22+0-24+6 weeks and 50 fetuses of 30+0-32+6 weeks, respectively. The characteristics of three-dimensional ultrasound were analyzed. The clinical and imaging data of 4 fetuses of 26+3-32+1 weeks with midgut volvulus were analyzed retrospectively. Results: The display rates of SMA and SMV were 93%in normal group by 3-DPDS and those in volvulus group were 4/4 and 3/4, respectively. The SMV trunk was parallel to and on the right side of the SMA in the normal group, while 3 cases in volvulus group showed the characteristic relationship of SMV swirling around SMA. Conclusion: 3-DPDS can be used to observe the spatial relationship of SMA and SMV visually in fetus during the second trimester and is of value to diagnose and predict the outcome of midgut volvulus.

Screening for hereditary tyrosinemia and genotype analysis in newborns
TONG Fan,YANG Rulai,LIU Chang,WU Dingwen,ZHANG Ting,HUANG Xinwen,HONG Fang,QIAN Guling,HUANG Xiaolei,ZHOU Xuelian,SHU Qiang,ZHAO Zhengyan
J Zhejiang Univ (Med Sci), 2019, 48(4): 459-464.   https://doi.org/10.3785/j.issn.1008-9292.2019.08.18
Abstract( 515 )   HTML( 11 )     PDF(977KB)( 233 )

Objective: To analyze the results of screening for hereditary tyrosinemia (HT) in newborns and its clinical features and genotype. Methods: The HT screening was conducted among 2 188 784 newborns from November 2013 to November 2018. The tyrosine (TYR)/ succinylacetone (SA) levels were detected by tandem mass spectrometry (MS-MS). The clinical characteristics, genetic results and following up data of identified patients were analyzed. Results: The normal ranges (0.5%-95.5%) of TYR and SA were 34.5-280.0 μmol/L and 0.16-2.58 μmol/L, respectively. Three HT cases were confirmed with a detection rate of 1:729 595. There was 1 case of tyrosinemia type Ⅰ (HTⅠ) (homozygous variations of c.455G>A in FAH gene), 1 case of tyrosinemia type Ⅱ(HTⅡ) (heterozygous variations of c.890G>T and c.408+1G>A in TAT gene), and 1 case of tyrosinemia type Ⅲ (HT Ⅲ) (homozygous variations of c.257T>C in HPD gene). The variations of c.890G>T, c.4081G>A of TAT and c.257T>C of HPD were novel. The positive predictive value of the screening was 3.4%. Case 1 (HTⅠ) with TYR and SA values of 666.9 μmol/L and 3.87 μmol/L respectively, presented cholestasis, mild elevated of liver enzyme and lactic acid, who were although fed with TYR and phenylalanine free milk, but died at 2 months of age. Case 2 (HTⅡ) with higher TYR (625.6 μmol/L) and normal SA at screening, received medical milk treatment; during the 7 months of follow-up the baby showed normal score of Bayley assessment and normal TYR without eye and skin symptoms. Case 3 (HT Ⅲ) with TYR of 1035.3 μmol/L and normal SA at screening; during the 29 months of follow-up the value of TYR fluctuated from 532.1 μmol/L to 1060.3 μmol/L due to irregular medical milk treatment, while the score of Bayley assessment was normal. Conclusions: HT is rare in the southern Chinese population, and the gene spectrum is scattered. Early treatment with nitisinone is recommended in children with HTⅠ, otherwise the prognosis is poor; the prognosis of children with HTⅡ is good when early treated with special diet; the prognosis of children with HTⅢ needs to be determined with more data.

18 articles