Objective:To analyze the clinical characteristics and SLC25A13 gene mutation in children with neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD).Methods:The data of 18 children diagnosed with NICCD in Xi′an Children′s Hospital from January 2014 to December 2018 were collected.The clinical manifestations, biochemical characteristics, SLC25A13 gene mutation and prognosis were analyzed.Results:All the 18 cases of NICCD were from North China and the age of initial diagnosis averaged(63.4±19.5)days.The clinical manifestations included jaundice(100%), light yellow or white stool(38.9%), growth retardation(27.8%)and so on.All patients had cholestasis.Of 18 cases, the levels of glutamyltranspeptidase, total bile acid and alpha fetoprotein were all increased, and serum albumin was decreased.Elevated aspartate aminotransferase(94.4%), elevated glutamic pyruvic transaminase(72.2%), prolonged prothrombin time(88.9%), hyperlactemia(83.3%), hypoglycemia(77.8%), anemia(66.7%)and other biochemical abnormalities were observed.Citrulline and other serum amino acids of all cases were elevated in blood samples by tandem mass spectrometry.The increase of 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate was found in 70%(7/10)urine samples by gas chromatography.Age was negatively correlated with total bile acid( r=-0.469, P=0.049), and positively correlated with blood ammonia, threonine, methionine, ornithine and tyrosine( r=0.472, 0.690, 0.698, 0.678 and 0.769, respectively, P<0.05). A total of 16 SLC25A13 gene mutations were detected, of them c. 851_854del(33.3%)and c. 1638_1660dup(19.4%)were the most common.c.1841+ 3_1841+ 4del, c.980_981del(p.E327Vfs*45)and c. 602A>T(p.E201V)were novel mutations.Among the 17 children who were followed up, 1 case died and 16 cases had normal biochemical parameters within 1 year. Conclusion:The characteristic biochemical changes are helpful for early recognition of NICCD.The prognosis of NICCD is good if the treatment is appropriate and timely.c.851_854del and c. 1638_1660dup are high-frequency mutations of SLC25A13 gene in north China.

OBJECTIVE: To analyze the clinical phenotypes and ATP7B gene variants among children patients with Wilson' s disease from Northwestern China. METHODS: The clinical features and variants of the ATP7B gene among 75 children with hepatic Wilson' s disease were retrospectively analyzed. RESULTS: Among the 75 cases, 4 were presymptomatic, 59 had isolated transaminase elevation, 12 had acute and/or chronic liver diseases. Nine children were found to harbor homozygous variants, 64 harbored compound heterozygous variants, and two only had heterozygous variants of the ATP7B gene. In total 49 variants were detected, with common variants including c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val) and c.2975C>T (Pro992Leu), which yielded allelic frequencies of 28.7%, 12.7% and 9.3%, respectively. Six novel variants were detected, which included c.1908dupC (p.Asn637Glnfs*118), c.4179_4180insC (p.Pro1394Profs*15), c.1604A>G (p.Glu535Gly), c.2278C>T (p.Pro760Ser), c.3008C>A (p.Ala1003Glu) and c.3532A>C (p.Thr1178Pro). Except for c.1604A>G (p.Glu535Gly), the remainder five were all predicted to be likely pathogenic. No significant correlation was found between genotype and phenotype among the patients. CONCLUSION The common mutation types of the ATP7B gene among patients with hepatic Wilson disease in Northwestern China are c.2333G>T (p.Arg778Leu), c.2621C>T (p.Ala874Val) and c.2975C>T (p.Pro992Leu), there is no significant correlation between their genotypes and phenotypes.
Copper-Transporting ATPases/genetics* ; Genotype ; Hepatolenticular Degeneration/genetics* ; Humans ; Mutation ; Phenotype ; Retrospective Studies

Objective:To investigate the epidemiological and clinical characteristics of visceral leishmaniasis (VL) in children, and to analyze the distinguishing features of VL associated hemophagocytic lymphohistiocytosis (HLH), so that to provide reference for the diagnosis and treatment of VL.Methods:Forty-one children with VL admitted to Xi′an Children′s Hospital from July 2012 to June 2021 were enrolled. The clinical data were retrospectively analyzed, including epidemiology, clinical manifestations, laboratory data, diagnostic methods, treatment regimens and outcomes. The patients were divided into VL group and VL+ HLH group according to whether combined with HLH or not, and the clinical characteristics and laboratory findings of the two groups were compared. Two independent samples t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Forty-one children with VL were from different provinces, including Shaanxi Province (70.73%(29/41)), Gansu Province (14.63%(6/41)), Shanxi Province (12.20%(5/41)) and Ningxia Hui Autonomous Region (2.44%(1/41)), and 87.80%(36/41) of them lived in rural areas. The peak age was >1.0 to 3.0 years old (63.41%(26/41)). They were sporadic throughout the year. The main clinical manifestations included fever (97.56%(40/41)), splenomegaly (95.12%(39/41)), lymphadenopathy (82.93%(34/41)) and hepatomegaly (60.98%(25/41)). The numbers of cases that Leishman-Donovan bodies were detected in the first, second and third bone marrow smears were 36, four and one, respectively. Anemia, thrombocytopenia and leukopenia detected by blood routine test were 100.00%(41/41), 78.05%(32/41) and 58.54%(24/41), respectively. There were statistically significant differences in the platelet count, lactate dehydrogenase, alanine aminotransferase, triglycerides, fibrinogen and ferritin between VL group (28 cases) and VL+ HLH group (13 cases) ( t=-2.56, t=2.64, Z=-2.66, t=7.15, t=-5.76 and t=3.86, respectively, all P<0.050). The proportions of hepatomegaly and hemophagocytes found in the bone marrow smears in VL group were both lower than those in VL+ HLH group, and the differences were both statistically significant ( χ2=4.47 and 10.93, respectively, both P<0.050). Twelve cases with VL+ HLH were treated with antimony (for six days) and intravenous immunoglobulin, and the others were treated with antimony only. The cure rates of the patients treated with antimony for one and two courses were 92.68%(38/41) and 4.88%(2/41), respectively. The dose of antimony was increased one third and treatment course was prolonged to eight days in one cured case. After (41.36±31.49) months of follow-up, three cases recurred after five to eight months of cure and all of them were cured after one more course of treatment with antimony. Conclusions:Children with VL are mainly distributed in rural areas. The common clinical manifestations are fever and involvement of reticuloendothelial system, which are not specific. The positive rate of Leishman-Donovan bodies found in bone marrow smears is high, and a few negative cases need repeated bone marrow aspiration. Standardized treatment with antimony for VL in children is effective, and combination therapy with immunoglobulin can be considered if patients with VL associated HLH. Very few cases may recur and antimony is still effective.

OBJECTIVE: To explore the genetic basis of a pedigree affected with Alagille syndrome (ALGS). METHODS: Targeted capture and next generation sequencing was carried out for the proband. Candidate variants were verified by Sanger sequencing among his family members. Their pathogenicity of the variant was predicted with bioinformatic analysis. Clinical characteristics and genotype-phenotype correlation were analyzed. RESULTS: The proband, his elder sister and mother were found to carry a heterozygous c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene, which may lead to premature termination of translation and a truncated protein with loss of function. The variant was unreported previously. The phenotypes of the proband (cholestasis, pulmonary artery stenosis and peculiar faces) have differed from those of his elder sister (cholestasis with pruritus, posterior embryonic ring of cornea) and mother (with no clinical manifestation). Cholestasis and peculiar face of the proband became insignificant with age. CONCLUSION The c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene probably underlay the ALGS in this pedigree with incomplete penetrance.
Aged ; Alagille Syndrome/genetics* ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

Mycoplasma pneumoniae pneumonia (MPP) complicated with cerebral venous sinus thrombosis (CVST) is rare.We retrospectively analyzed the clinical data of two patients with refractory mycoplasma pneumoniae pneumonia (RMPP) complicated with CVST who were hospitalized in Xi′an children′s Hospital from December 2018 to April 2019, inquired the relevant literature, analyzed the clinical diagnosis and treatment characteristics, and discussed the diagnosis and treatment measures of RMPP complicated with CVST.Two cases were 6-year-old girls with fever and cough as the main symptoms.After physical examination, the respiratory sounds of the affected lung decreased, and the sounds of phlegm and dampness could be heard in both lungs.Mycoplasma pneumoniae (MP) antibody and RNA were positive.Chest CT showed lobar pneumonia with a large number of pleural effusion.The effect of macrolide antibiotics anti infection treatment was not good.Headache symptoms occurred during the course of the disease, and serum D-dimer increased significantly.Brain MRI showed CVST, including 1 case with lower extremity pain, and B-ultrasound showed right lower extremity arterial embolism.After anti infection, thrombectomy, anticoagulation and symptomatic treatment, 2 cases were discharged.When children with MPP, especially those with RMPP, have extracranial thrombosis and/or neurological symptoms, accompanied by elevated serum D-dimer, the possibility of CVST should be considered, and brain MRI examination should be performed in time to confirm and actively treat, which can reduce or avoid the occurrence of sequelae.Thrombosis may be related to excessive inflammatory reaction and vascular endothelial injury caused by MP infection.

OBJECTIVETo understand the age distribution of pertussis patients admitted in the children hospital and to analyze the source of infection as well as its transmission patterns.

METHODSPatients visiting to the Children Hospital and epidemiologically related cases during Feb. 2012 to Aug. 2013 were tested to confirm the diagnosis. Excel 2007 software was used to analyze the age distribution and clinical symptoms of clinic cases, the source of infection or subsequent cases.

RESULTS165 out of 254 clinically suspicious pertussis cases and 38 out of the 54 epidemiologically related cases were confirmed of having pertussis infection. There were 138 (83.6%) cases under 1 year of age in the confirmed clinical cases and 36 (94.7%) cases older than 20 years of age among the confirmed epidemiologically related pertussis cases. All the confirmed epidemiologically related cases were misdiagnosed or missed for diagnosis. As the source of pertussis infection in confirmed clinical cases, parents played an imported role among 25 of the 32 cases. Transmission from infants and/or little children to adults were also observed in this study.

CONCLUSIONInfants accounted for the most among the pertussis patients that visiting the clinics. Adults, being misdiagnosed or missed diagnosed, were the main sources of infection to infants. Epidemics of pertussis occurred under family aggregation. Further study was in need to develop the proper strategy for pertussis booster vaccination.

Adult ; Age Distribution ; Child ; Child, Preschool ; Delayed Diagnosis ; Diagnostic Errors ; Family ; Humans ; Infant ; Whooping Cough ; epidemiology ; transmission