Characteristics of plasma Epstein-Barr virus DNA in children with primary infection / 中华儿科杂志

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

Homozygous familial hypobetalipoproteinemia caused by APOB gene variations: a case report and review of literature / 中华儿科杂志

Objective: To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. Methods: The clinical, laboratory, genetic, and liver histology data of a boy with Ho-FHBL managed in the hepatology ward of the Children's Hospital of Fudan University in May 2021 were retrospectively analyzed. The literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to May 2022) with "familial hypobetalipoproteinemia" or "hypobetalipoproteinemias" or "hypo beta lipoproteinemia" or "hypolipoproteinemias" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of Ho-FHBL caused by APOB gene variations. Results: The male patient was admitted to the hospital due to abnormal liver function tests for 8 months at the age of 4 years and 6 months. Blood biochemistry showed transaminitis and abnormally low serum levels of lipids. Liver biopsy revealed fatty liver with inflammation and early cirrhosis (Brunt score was F3G2S4). Whole exome sequencing revealed two novel variants of APOB gene (c.3745C>T, p.Q1249 * from the father and c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT, p.T1530Kfs * 12 from the mother). He was diagnosed as Ho-FHBL caused by APOB gene compound heterozygous variations. Literature search retrieved 36 English literatures and 0 Chinese literature. A total of 55 (23 males and 32 females) Ho-FHBL cases, including this one, were caused by 54 APOB gene pathogenic variants (23 frameshift, 15 nonsense, 7 missense, 8 splice and 1 gross deletions). The age of the last follow-up was between 1 month and 75 years. Among them, 28 cases had lipid malabsorption, 19 cases had early dysplasia, 12 cases had no symptoms. Twenty-one patients had symptoms related to fat soluble vitamin deficiency, including 14 cases of acanthocytosis, 10 cases of neurological symptoms, and 6 cases of ocular lesions. Thirty-four patients had liver involvement, including 25 cases of elevated transaminase, 21 cases of fatty liver, 15 cases of hepatomegaly, 9 cases of liver fibrosis, 3 cases of liver cirrhosis, 1 case of hepatic hemangioma and 1 case of liver neoplastic nodule. Conclusions: The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. Patients may have lipid malabsorption and (or) early dysplasia, or symptom-free. Liver involvement is common.

Liver transplantation for the treatment of acute liver failure in 3 cases with NBAS gene deficiency and literature review / 中华儿科杂志

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.

Analysis of 6 cases with hepatocerebral mitochondrial DNA depletion syndrome and literature review / 中华儿科杂志

Objective: To explore the clinical features of hepatocerebral mitochondrial DNA depletion syndrome (MDS). Methods: The clinical data of 6 hepatocerebral MDS patients diagnosed in the Jinshan Hospital of Fudan University from January 2012 to December 2019 were retrospectively collected and analyzed. Related literature published before January 2020 were searched with the key words of "DGUOK""MPV17""POLG""C10orf2" in PubMed, China national knowledge infrastructure (CNKI) and Wanfang database. Results: All the 6 hepatocerebral MDS cases were male. The age of onset ranged from 3 days to 8 months. The most common initial symptoms were cholestasis and developmental retrogression. The main clinical manifestations included hepatomegaly (4 cases), hypotonia (3 cases), growth retardation (4 cases), cholestasis (5 cases), coagulopathy (5 cases), hypoalbuminemia (3 cases), hypoglycemia (4 cases), hyperlactacidemia (5 cases), and abnormal blood metabolism screening (6 cases). The isotope hepatobiliary imaging revealed no gallbladder and intestinal tract development within 24 hours in 2 patients. Regarding the cranial imaging examination, the head CT found widening of the extracranial space in 1 case, the brain magnetic resonance imaging (MRI) found ventricular enlargement in 2 cases, and the brain ultrasound found peripheral white matter injury in 1 case. Two cases were lost to follow-up, one died of liver failure, and three died of multiple organ failure due to aggravated infection. Among the 6 cases, there were 3 with MPV17 variation (c.182T>C and c.279G>C were novel), 1 with POLG variation (c.2993G>A was novel), 1 with DGUOK variation (c.679G>A homozygous mutation, parthenogenetic diploid of chromosome 2) and 1 with C10orf2 variation (c.1186C>T and c.1504C>T were novel). The literature review found that 129, 100, 51 and 12 cases of hepatocerebral MDS were caused by DGUOK, MPV17, POLG and C10orf2 gene variations, respectively. And the most common clinical manifestations were liver dysfunction presented with cholestasis and elevated transaminase, metabolic disorders including hypoglycemia and hyperlactacidemia, and diverse neurologic symptoms including developmental retardation, hypotonia, epilepsy and peripheral neuropathy. Besides, 1/3 of the patients with C10orf2 variation developed renal tubular injury. Conclusions: Hepatocerebral MDS mainly present with liver dysfunction, metabolic disorder and neuromuscular impairment. Different genotypes show specific clinical manifestations.

Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Mutation analysis of FAH gene in patients with tyrosinemia type 1 / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and mutations of the FAH gene.</p><p><b>METHOD</b>Clinical records of two cases were collected, and diagnosis was made according to the diagnostic criteria of the International Organization for Rare Disorders (NORD). Genomic DNA was extracted from peripheral blood leukocytes with QIAamp DNA Mini Kit. The DNA extracts were subjected to direct sequencing for 14 exons together with adjacent fragments of FAH gene using ABI Prism 3730 Genetic Analyzer (Applied Biosystems, Foster City, CA) after PCR based on genomic DNA. The mutation source was verified by analyzing parents' exons corresponding to patients' mutation exons. The homology between human FAH enzyme and that of other species was surveyed using software Clustal X(European Bioinformatics Institute, Hinxton, Saffron Walde, UK). Polyphen (Polymorphism Phenotyping), available online, were used to predict possible impact of an amino acid substitution on structure and function of FAH enzyme. Polyphen calculates position-specific independent counts (PISC) scores for two amino acid variants in polymorphic position. A PISC scores that differ by > 2 were regarded as indicating the probability of damaging variants.</p><p><b>RESULT</b>Patient 1 was a 5 months and 21 days-old boy who suffered from persistent diarrhea, hepatomegaly, ascites; Alpha-fetoprotein > 1210 µg/L, levels of tyrosine in blood and succinylacetone in urine were 110.8 µmol/L and 83.7 µmol/L. His sister suffered from tyrosinemia type 1. Direct sequencing showed a G to A transition in CDS position 455 and 1027. He was compound heterozygous for the mutation c.455G > A/c.1027G > A, which predicts a change from tryptophan to a stop codon (TGG > TAG) at position 152 (W152X) and a change from glycine to arginine (GGG > AGG) at position 343 respectively. Patient 2 was a 6 year and 1 month-old girl with late-onset rickets who had signs of hepatosplenomegaly, rachitic rosary, windswept knees. Hypophosphatemia and alkaline phosphatase 1620 IU/L were detected. Alpha-fetoprotein 412.8 µg/L, levels of tyrosine in blood and succinylacetone in urine were 835.8 µmol/L and 27.48 µmol/L. Rickets did not improve after administration of calcium and vitamine D3. She is homozygous for the mutation c.1027G > A/c.1027G > A, which predicts G343R. The parents were mutation carriers. Analysis by Clustal X on the alignment of amino acids residual reservation among different species showed that the locative amino acid was highly conserved. Polyphen software predicted G343R was probably damaging (PISC score 3.235).</p><p><b>CONCLUSION</b>Children with tyrosinemia type 1 can have manifestations of persistent diarrhea or late-onset rickets. Physical examination can reveal hepatosplenomegaly, laboratory tests indicate markedly elevated serum concentration of alpha-fetoprotein and alkaline phosphatase in plasma and succinylacetone in urine, other members in family may have tyrosinemias or parents are consanguineous. Mutations c.455G > A and c.1027G > A can be detected in FAH gene of Chinese children.</p>

Significance of V444A polymorphism of ABCB11 gene in neonatal cholestasis / 中华实用儿科临床杂志

Objective To explore the association between one common variant in ABCB11-1331T ＞ C (V444A) and neonatal cholestasis.Methods One hundred and ninety-two children with neonatal cholestasis were enrolled as case group,and 196 healthy children were selected as healthy control group.The SNP site of V444A was tested by fluorescent quantitative PCR.Fisher's exact test was performed to detect the differences in allele and genotype distribution between the 2 groups.Wilcoxon rank-sum test was used to test the differences of total bilirubin,total bile acid,γ-glutamyl transpeptidase levels among the patients with different genotypes.Results TT,TC and CC genotypic distribution of V444A were not significantly different between patients and controls (P =0.530).The T allele in the case group accounted for 29.9％,in the healthy control group accounted for 26.3％,there was no significant difference between the 2 groups(OR =1.12,P =0.264).Total bilirubin,total bile acid,γ-glutamyl transpeptidase levels in patients with different genotypes of V444A were also not statistically different (all P ＞ 0.05).Conclusion Only V444A variant may have no impacts on neonatal cholestasis.

Characteristics of the plasma amino acid spectrum of neonatal intrahepatic cholestasis caused by citrin deficiency / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the plasma amino acid spectrum in infants more than 1-year-old with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in order to identify potential diagnostic markers of NICCD.</p><p><b>METHODS</b>Infants less than 1 year of age who had been referred to our hospital for investigation of suspected conjugated hyperbilirubinemia between June 2003 and June 2009 were eligible for enrollment. A total of 182 infants were enrolled and divided into three groups: infants diagnosed with NICCD (n = 24), according to gene testing and/or western blotting results; infants diagnosed with biliary atresia (BA; n = 20), according to intra-operative cholangiography findings; and infants diagnosed with idiopathic neonatal intrahepatic hepatitis (INH; n = 138), according to exclusionary findings for diseases affecting the extrahepatic biliary system and no positive serology results to indicate infections with hepatitis B, C, A or E, toxoplasmosis, rubella, herpes simplex, human immunodeficiency virus-1, or syphilis. The plasma amino acid spectrum of each infant was analyzed by tandem mass spectrometry (MS/MS). The concentrations of 18 amino acids, as well as the ratio of each amino acid to total amino acids, were compared among the three groups. Selected ratios of amino acids were analyzed by receiver operating characteristic (ROC) curve analysis.</p><p><b>RESULTS</b>Compared with the BA and INH groups, the NICCD group had significantly lower levels of alanine (Ala; 175.7 and 205.7 vs. 136.3 mumol/L, P = 0.0001), aspartic acid (Asp; 47.5 and 43.1 vs. 31.55 mumol/L, P = 0.0041), glutamic acid (Glu; 276.16 and 263.24 vs. 175.71 mumol/L, P = 0.0075) and tryptophan (Trp; 41.90 and 47.97 vs. 28.51 mumol/L, P = 0.0003), but significantly higher levels of methionine (Met; 28.24 and 29.35 vs. 71.40 mumol/L, P = 0.0390), tyrosine (Tyr; 55.8 and 57.02 vs. 116.81 mumol/L, P = 0.0072) and citrulline (Cit; 15.09 and 15.65 vs. 97.42 mumol/L, P = 0.0001). The ratio of each amino acid to total amino acids showed the same trends for the NICCD group. The calculated areas under the ROC curves of the ratios of Cit, Tyr, and Met to the total amino acids were 0.874 (95% CI: 0.752 - 0.996), 0.814 (95% CI: 0.706 - 0.923), and 0.705 (95% CI: 0.535 - 0.875) respectively. The calculated area under the ROC curve of the ratio of Cit to Ala was 0.893 (95% CI: 0.781 - 1.005), and when the cut-off value of the ratio of Cit to Ala was 0.14 for diagnosis of NICCD, the sensitivity and specificity were 75% and 95% respectively.</p><p><b>CONCLUSION</b>The plasma amino acid spectrum may represent a diagnostic indicator for NICCD, particularly the ratio of Cit to Ala.</p>

Personal experience in pediatric emergency medicine training in Canada and China / 中华医学杂志(英文版)

Currently, pediatric emergency medicine (PEM) as practiced in many developed countries is different from ours in China. Chinese pediatric emergency medicine is just children's internal medicine and does not include general surgery, ear-nose-throat, etc. If children have an emergency condition that require specialized treatments they need to go to different departments. However in Canada, the pediatric emergency physicians will first treat the patients whatever the condition, then, if it is a complicated sub specialty problem, they will consult the specialist or let the patient see the specialist later. In addition, resuscitation is done in the pediatric intensive care unit (PICU) in China, but it is done in the emergency room in Canada. This article compares the differences in the pediatric emergency systems in Canada and China and also introduces the international standard system of pediatric triage.

A new frame-shifting mutation of UGT1A1 gene causes type I Crigler-Najjar syndrome / 中华医学杂志(英文版)

We present a case of severe persisting unconjugated hyperbilirubinemia in a Uigur infant boy, eventually diagnosed as Crigler-Najjar syndrome type I. DNA analysis of his blood of the UGT1A1 gene sequence demonstrated that he was homozygous for an insertion mutation causing a change of the coding exons with a frame-shift, resulting in the substitution of 27 abnormal amino acid residues in his hepatic bilirubin uridine diphosphoglucuronyl transferase enzyme. Both of his parents were heterozygous for the same mutation. A novel frame-shifting mutation of the UGT1A1 gene was found, confirming the diagnosis of Crigler-Najjar syndrome type I for this patient.

The reassessment of the diagnostic value of 24-hour urinary copper excretion in children with Wilson's disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To reassess the diagnostic value of 24 hour urinary copper excretion in children with Wilson disease (WD).</p><p><b>METHODS</b>From July 2005 to June 2007, inpatients over three years old in a pediatric liver center were assigned into WD and non-WD group.</p><p><b>RESULTS</b>94 patients, including 26 cases in WD and 68 in non-WD group, were enrolled in this study. The median of 24 h urinary copper excretion was 98.5 microg in WD group and 25.8 microg in the non-WD group (Z = -6.111, P equal to 0.000). The area under receiver operator curve (ROC) was 0.909 (95% CI: 0.839-0.979, P equal to 0.000). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6% and 93.9% respectively using 52.0 ug as a cutoff value, and 50.0%, 97.1%, 84.0%, 86.7% and 83.5% using 100 microg as a cutoff value. The goodness of fitness of 52 microg criteria was significantly higher than 100 microg criteria (kappacoefficient 0.760, 0.541 respectively, P equal to 0.000).</p><p><b>CONCLUSION</b>Comparing to 100, 52 microg of 24 h urinary copper excretion as a cutoff value significantly improves the sensitivity and accuracy for diagnosing WD in children.</p>

Clinical characteristics of autoimmune hepatitis in 11 children / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of autoimmune hepatitis (AIH) in children so as to improve the awareness of the disease.</p><p><b>METHOD</b>The medical records of 12 children who were clinically diagnosed as AIH between 2004 and 2008 were reviewed. The scoring system of the International Autoimmune Hepatitis Group (IAIHG) for diagnosis of AIH was used to confirm the diagnoses. Clinical manifestations, laboratory examinations, liver pathology results and prognosis were retrospectively analyzed.</p><p><b>RESULT</b>Eleven patients were diagnosed as AIH by the scoring system and 10 of them were type I, one had not been typed. The average time from onset to diagnosis was (7.5 ± 7.4) months. Seven patients (63.6%) had acute onset, among them 2 cases progressed to subacute severe hepatitis, 3 (27.3%) had deliquescence onset and 1 (9.1%)was complicated with hepatic cirrhosis. Levels of serum globulin and IgG were tested and were higher in 10 cases (90.9%) with average (39.4 ± 7.4) g/L and (31 ± 12) g/L respectively. Antinuclear antibodies (ANA) were measured positive in 10 cases, and 1 was anti-smooth muscle antibody (SMA) positive. Liver-kidney microsomal antibody (LKM-1) and anti-mitochondrial antibody (AMA) were detected in none of them. The liver pathology of 11 cases could be divided into acute and chronic hepatitis in 5 and 6 cases, respectively. Severe submassive liver necrosis and severe fibrosis were identified in 3 cases respectively. Lymphocytes infiltration, interfaces hepatitis and rosette-like annulation of hepatocytes were found in 81.8%, 36.4%, and 18.2% of cases on liver pathology. Eleven patients were followed up with therapy of single glucocorticoids or glucocorticoids combined with immunosuppressive agents. The disease of 2 cases deteriorated and 3 cases died. One case was still under therapy, 1 case was stabilized and 4 cases had recurrence.</p><p><b>CONCLUSION</b>The children with AIH had diverse symptoms, signs, onsets and laboratory test results. The liver pathological changes were less typical. Rate of misdiagnosis was high in early stage. Prognosis was poor in most cases even though properly treated. Therefore close attention needs to be paid to children with AIH.</p>

Clinical features of hepatolenticular degeneration in children / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To review the clinical features and liver pathology in children with hepatolenticular degeneration.</p><p><b>METHODS</b>Clinical manifestations and results of lab tests and liver biopsies of 97 cases diagnosed as hepatolenticular degeneration in Children's Hospital of Fudan University from Jan 1990 to Nov 2006 were reviewed.</p><p><b>RESULTS</b>Manifestations of liver malfunction were the most common reason (74%) for their clinic visits. All cases showed liver involvement and nervous system involvement was found in 45%. Positive K-F rings were detected in 63 of 95 cases; ceruloplasmin level was low in 91 of the 94 cases, and 24 hour urinary copper excretion exceeded 100 microg in 25 out of 37 cases who had had this test. Seventeen cases had a liver biopsy. Various levels of inflammation and fibrosis were noted in all 17 biopsies; 8 of the 17 also had steatosis and 3 of the 17 also had glycogen accumulation.</p><p><b>CONCLUSION</b>Liver abnormality is a consistent feature in children with hepatolenticular degeneration. Corneal K-F rings, serum ceruloplasmin and the 24-hour urinary copper test have limited values for an early diagnosis of the disease. Liver pathology can be a reference in the diagnosis of hepatolenticular degeneration.</p>

SLC25A13 gene mutations in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore whether SLC25A13 gene mutation exists and what is its mutation spectrum in mainland Chinese infants with intrahepatic cholestasis and abnormal blood amino acids.</p><p><b>METHODS</b>Blood amino acids were analyzed by mass chromatographic analysis in infants referred to Fudan University Children's Hospital from June 2003 to June 2007 for investigations of intrahepatic cholestasis of unknown origin. SLC25A13 gene mutations were studied in 14 children whose serum levels of citrulline and/or methionine were at least two times above the upper normal range. In patients in whom only one mutation was detected, all other exons and their neighboring sequences were then analyzed.</p><p><b>RESULTS</b>Eight patients with SLC25A13 gene mutations, including 2 with compound heterozygous mutation 851del4/1638ins23, one with homozygous mutation 851del4/851del4, one with compound heterozygous mutation 851del4/R184X, one with homozygous mutation IVS6+1G more than A/IVS6+1G more than A, and 3 with heterozygous mutation 851del4 were found.</p><p><b>CONCLUSIONS</b>SLC25A13 gene mutations exist in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids. Their mutation spectrum is different from that in Japan. 851del4 is the most common mutation in our study. IVS6+1G more than A is a mutation that has not been reported before.</p>

Relationship between interleukin-12B gene + 1188 polymorphism and the susceptibility to hepatitis B virus intrauterine infection / 中华传染病杂志

10 mU/L (GroupⅡ,71 cases) when they were one year old.There were 40 healthy children in control group. The genomic DNA from the peripheral blood was extracted and polymerase chain reaction (PCR) and sequencing were employed to detect the IL-12B gene 3′UTR+1188 SNP.Results The frequency of AA,AC and CC genotype in GroupⅠwere 25.7%,44.3% and 30.0% respectively,and 36.6%, 47.9% and 15.5% in GroupⅡ,48.8%,39.0%,12.2%,in control group,respectively.The differ- ence of frequency of CC genotype and non-CC genotype between GroupⅠand GroupⅡwas significant (x~2=17.078,P

Study on the S region gene mutation of hepatitis B virus during prevention of HBV transmission in uterus with hepatitis B immunoglobulin / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the relationship between hepatitis B immunoglobulin (HBIG) injection before delivery and hepatitis B virus (HBV) S gene mutation.</p><p><b>METHODS</b>18 neonates infected with HBV in uterus and their mothers were divided to a) HBIG group (8) in which their mothers received HBIG injection before delivery and b) control group (10) in which their mothers never received any treatment HBV DNA fragments were amplified by nest-PCR from sera of these neonates and their mothers. S gene region of these HBV DNA fragments were directly sequenced and data on mutations was analyzed.</p><p><b>RESULTS</b>There was no significant difference on nucleotide and amino acid changes in the S gene between the HBIG group and the control group. The majority HBV strains of newborn (17/18) were identical to their mother's dominant strains before delivery, including four mutation HBV strains. Among 18 newborns with HBV intrauterine infection, 12 were infected by B type (adw2), and 6 by C type (adrq+).</p><p><b>CONCLUSION</b>Mothers who were asymptomatic HBsAg carrier and received injections ofHBIG before delivery would not be influenced by HBV S gene mutation. HBV intrauterine transmission with or without gene mutation might occur in the third-trimester of pregnancy. Gene mutation of HBV was not the main factor in intrauterine transmission of HBV.</p>

ABCB11 Gene Variation and Cholestatic Diseases / 实用儿科临床杂志

ABCB11 gene encodes bile salt export pump (BSEP).It is almost exclusively expressed in the canalicular microvilli of liver.It is the principal conveyor of bile acids from hepatocyte cytoplasm into bile canaliculus.It is clearly that BSEP defects can induce progressive familial intrahepatic cholestasis type 2 and benign recurrent intrahepatic cholestasis type 2.ABCB11 gene variation are also responsible for intrahepatic cholestasis of pregnancy,drug-induced cholestasis,primary sclerosis cholangitis and primary bile cirrhosis.This paper reviewed the association of ABCB11 gene variation and these diseases.

Characteristics and expression of Mip5, a novel gene associated with myocardial ischemia/reperfusion in rats / 中南大学学报(医学版)

OBJECTIVE@#To determine the characteristics of a novel gene Mip5 (GenBank accession number AY553870) and its expression under physiological and pathological conditions.@*METHODS@#The characteristics of Mip5 were analyzed by bioinformatic programs including BLAST, spidey, psort, ClustalW and so on. RT-PCR was performed to detect Mip5 expression.@*RESULTS@#Bioinformatic analysis showed that Mip5 gene lied in the 13th chromosome and contained 8 exons and 7 introns, its open reading frame contained 909 bp and its protein production was 302 amino acid residues including 6 kelth domains. Under normal conditions, MIP5 expressed abundantly in the heart, brain and kidney, but its expression could not be detected in the liver and muscle. Expression of Mip5 gene was increased significantly after ischemia-reperfusion compared with the sham groups, and reached its peak at 3 h and recovered at 12 h after the reperfusion. Conclusion Mip5 gene is a novel gene containing a putative open reading frame of 302 amino acids residues and may play an important role in rat cardiomyocytes suffering ischemia processing.

Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection.</p><p><b>METHODS</b>This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group I); and immune effective group (group II) and non high risk children belonged to the control group. Four gene SNP sites of TNF-alpha -238, IFN-gamma +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR).</p><p><b>RESULTS</b>The significant differences of TNF-alpha -238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) and between group I and the control group (chi(2) = 9.513, P < 0.05). No evident differences of TNF-alpha -238 A were found between group II and control group (chi(2) = 0.047, P > 0.05); the significant differences of IFN-gamma +874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the control group (chi(2) = 5.199, P < 0.05). No evident differences were found between group II and the control group (chi(2) = 0.602, P > 0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), also group I and the control group (chi(2) = 0.584, P > 0.05), and the group II and the control group (chi(2) = 0.004, P > 0.05) respectively; The significant differences of IL-10 -1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but the significant differences were not found between group I and the control group (chi(2) = 1.759, P > 0.05).</p><p><b>CONCLUSIONS</b>This study suggested the possibility that the TNF-alpha -238 A allele and IFN-gamma +874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection.</p>

Detection of enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Shanghai, 2002 / 中华儿科杂志

<p><b>OBJECTIVE</b>It was noticed that coxsackievirus A16 (CA16) and enterovirus 71 (EV71) were two major etiological agents of hand, foot and mouth disease (HFMD) in children. Recently there were several large outbreaks of HFMD in the Asia-Pacific region, and there was a propensity to cause severe complications or death in children under 5 years of age. The severe forms were associated with EV71 infection. Although epidemics of HFMD have been reported in the mainland of China, few reports about EV71 as the pathogen of HFMD epidemics are available. The present study was conducted to investigate the causal agent of an HFMD epidemic in children in Shanghai from April to June of 2002.</p><p><b>METHODS</b>Totally 102 specimens (including vesicle fluid, stool and throat swabs) were collected from 72 patients with HFMD. The specimens were inoculated into Vero and/or RD cells. At first all the isolates were respectively neutralized by the RIVM pools of enterovirus antiserum, the type-specific antisera to EV71 or to CA16. Secondly all untyped isolates were tested by RT-PCR assay with two specific primer pairs for VP1 genes of EV71 and CA16 respectively. The EV71 and CA16 were identified depending on the size of PCR products. Sequence analyses of VP1 genes of 9 virus strains were performed by the laboratory of China CDC.</p><p><b>RESULTS</b>Viruses were isolated from 91 specimens from 67 patients. Serotyping by neutralization failed for all the isolates. But the RT-PCR results indicated that the viruses isolated from 78 specimens from 58 patients were identified as positive for CA16 and the isolates from 13 specimens from 9 patients were identified as positive for EV71, the ratio between CA16 and EV71 was 6.4:1. The results of sequence analyses were consistent with those of PCR assay. Two EV71 strains isolated in this study belonged to a new lineage (C4) within genogroup C. One patient with EV71-associated HFMD had a complication of encephalitis with convulsion, shock, coma and dyspnea.</p><p><b>CONCLUSION</b>CA16 and EV71 were the primary causes of HFMD during the epidemic. It was the first report of EV71-associated severe encephalitis occurred in patients with HFMD in Shanghai.</p>