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BACKGROUND The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype. CASE SUMMARY An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant’s liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now. CONCLUSION Based on the infant’s clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.

Purpose This study aims to report the clinical features of an infant with CGL in a Chinese Zhuang ethnic family, whose family members were discovered to carry new pathogenic mutations in the BSCL2. Patients and methods In this study, we report clinical and molecular investigations of CGL disease in a family of 4 members (parents and two sons). We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Results The proband presented with skin pigmentation, hypertriglyceridemia and diabetes. WES identified a previously unreported compound heterozygous mutation in the BSCL2 (c.545_546insCCG heterozygous mutation and exon 3 heterozygous deletion) in the proband. His mother is a heterozygous carrier of the c.545_546insCCG mutation and his father and brother are carriers of the exon 3 heterozygous deletion. Conclusion Compound heterozygous mutation of the BSCL2 (new c.545_546insCCG heterozygous mutation and new exon 3 heterozygous deletion) was detected in the proband with characteristic clinical manifestations of CGL2.

To develop a noninvasive model to predict significant fibrosis in children with chronic hepatitis B (CHB). A total of 116 CHB pediatric patients who underwent liver biopsy were included in the study. Liver histology, which is the gold standard for assessing fibrosis, was performed. Blood routine examination, coagulation function, liver biochemistry, viral serology, and viral load were analyzed. Receiver operating characteristic curve analysis was used to analyze the sensitivity and specificity of all possible cut-off values. Based on the correlation and difference analyses, 7 available clinical parameters (total bile acid, gamma-glutamyl transpeptidase [GGT], aspartate transaminase, direct bilirubin to total bilirubin ratio, alanine aminotransferase, prealbumin [PA], and cholinesterase) were included in the modeling analysis. A model to predict significant liver fibrosis was derived using the 2 best parameters (PA and GGT). The original model was Y=−1.803 ln PA(mg/L)+0.769lnGGT(U/L)+6.436. After the mathematical calculation, the G index=600 × GGT/PA2 predicted significant fibrosis, with an area under the receiving operating characteristics (AUROC) curve of 0.733, 95% confidence interval (0.643–0.811). The AUROC of the G index (0.733) was higher than that of aminotransferase to platelet ratio index (APRI) (0.680) and Fibrosis index based on 4 factors (FIB-4) (0.601) in predicting significant fibrosis in children with CHB. If the values of the G index were outside the range of 0.28 to 1.16, 52% of children with CHB could avoid liver biopsy, with an overall accuracy of 75%. The G index can predict and exclude significant fibrosis in children with CHB, and it may reduce the need for liver biopsy in children with CHB.

Intestinal myiasis caused by fly larvae parasitic in gastrointestinal tract was rare reported in children. We reported an infant with bloody diarrhea caused by intestinal myiasis. A 1 year and 7 months old boy presented with the only symptom of bloody diarrhea of unknown origin. In the second week of onset, numerous moving worms were observed in the bloody stool after bowel preparation with polyethylene glycol for colonoscopy. The bloody diarrhea disappeared after 1 week of combined therapy with albendazole and metronidazole. On follow-up after 6 months, the patient remained well without bloody diarrhea. In conclusion, intestinal myiasis being a rare disease that is very challenging to diagnose, physicians should remember it when they receive cases of bloody diarrhea with non-specific symptoms without any apparent cause.

Purpose This study aims to report the clinical features of an infant with CGL in a Chinese Zhuang ethnic family, whose family members were discovered to carry new pathogenic mutations in the BSCL2. Patients and methods In this study, we report clinical and molecular investigations of CGL disease in a family of 4 members (parents and two sons). We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Results The proband presented with skin pigmentation, hypertriglyceridemia and diabetes. WES identified a previously unreported compound heterozygous mutation in the BSCL2 (c.545_546insCCG heterozygous mutation and exon 3 heterozygous deletion) in the proband. His mother is a heterozygous carrier of the c.545_546insCCG mutation and his father and brother are carriers of the exon 3 heterozygous deletion. Conclusion Compound heterozygous mutation of the BSCL2 (new c.545_546insCCG heterozygous mutation and new exon 3 heterozygous deletion) was detected in the proband with characteristic clinical manifestations of CGL2.

Rationale: Glycogen storage disease (GSD) type VI is a rare disease caused by the inherited deficiency of liver phosphorylase. Patient concerns: The proband, a 61-month-old Chinese boy, manifested intermittent hematochezia, growth retardation, hepatomegaly, damage of liver function, mild hypoglycemia, and hyperlactatemia. The other patient was a 107-month-old Chinese girl with growth retardation, hepatomegaly, mild hypoglycemia, and hyperlactatemia. In order to further confirm the diagnosis, we conducted a liver biopsy and detected blood samples for their gene using IDT exon chip capture and high-throughput sequencing. Diagnoses: According to the clinical symptoms, physical examination, laboratory examinations, liver biopsy, and the genetic test finding, the 2 patients were diagnosed GSD VI. Interventions: They were treated mainly with uncooked cornstarch. Outcomes: There were 2 mutations of PYGL gene in this pedigree. c.2467C>T (p. Q823X) and c.2178-2A>C occurred both in the proband and his second sister. Lessons: As a novel mutation, c.2178-2A>C enriches the mutation spectrum of PYGL gene. The different degrees of elevated lactate is an unusual phenotype in GSD VI patients. It is not clear if this is caused by the new mutation of c. 2178-2A > C. Long-term complications remains to be observed.

Background Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors and is most often attributable to mutations in the lipoprotein lipase (LPL) gene. Objectives The aim of this study was to identify rare mutations in the LPL gene causing severe hypertriglyceridemia. Methods A Chinese infant who presented classical features of severe hypertriglyceridemia recruited for DNA sequencing of the LPL gene. The pathogenicity grade of the variants was defined based on the prediction of pathogenicity using in silico prediction tools. Review some studies to understand the molecular mechanisms underlying the severe hypertriglyceridemia. Results We identified a rare mutation in the LPL gene causing severe hypertriglyceridemia: a nucleotide substitution (c.836T>G) resulting in a leucine to arginine substitution at position 279 of the protein (p.Leu279Arg).The pathogenicity of the variant was predicted by in silico analysis using PolyPhen2 and SIFT prediction programs, which indicated that mutation p.Leu279Arg is probably harmful. We have also reviewed published studies concerning the molecular mechanisms underlying severe hypertriglyceridemia. A missense mutation in the 6 exon of the LPL gene is reportedly associated with LPL deficiency. Conclusions We have here identified a rare pathogenic mutation in the LPL gene in a Chinese infant with severe hypertriglyceridemia.

To analyze the effects of ursodeoxycholic acid (UDCA) on the mRNA expression of multidrug resistance protein 3 (MDR3) and farnesoid X receptor (FXR) in infants with cholestatic hepatitis.Twenty-eight infants who were diagnosed with cholestatic hepatitis between July 2008 and July 2010 were included in the study. These patients received treatment with UDCA. The mRNA expression levels of MDR3 and FXR were measured by real-time quantitative RT-PCR with SYBR Green I, before and after treatment with UDCA.After treatment with UDCA, the infants with cholestatic hepatitis had significantly decreased serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and gamma-glutamyltransferase (P0.05) and significantly increased mRNA expression of MDR3 (P0.05). No significant change in mRNA expression of FXR was observed, however (P0.05).UDCA improves liver function indices in infants with cholestatic hepatitis, which may be related to up-regulated mRNA expression of MDR3.

To study hepatic NF-κB level following endotoxemic liver injury, and its relationship with hepatic TNF-α and IL-6 levels in young rats.Forty 18-day-old rats were randomly assigned to a normal control and an endotoxemia group. Endotoxemia was induced by lipopolysaccharide injection (LPS, 5 mg/kg). The endotoxemia group was subdivided into four groups sampled at 2, 6, 12 and 24 hrs after LPS injection (n=8 each). Pathological changes in liver cells were observed under a light microscope. TNF-α and IL-6 levels in liver tissue homogenates were measured using ELISA. Reitman-Frankel was used to measure serum ALT concentrations. NF-κB activation level in liver tissues was detected by immunohistochemistry.Liver tissue injury was the most obvious 6 hrs after LPS injection under the light microscope, and the damage rating of liver tissues was significantly higher in the endotoxemia group than that in the normal control group at all time points (P0.05). ALT levels in the endotoxemia group were significantly higher than those in the normal control group 6, 12 and 24 hrs after LPS injection (P0.05). NF-κB p65 protein expression in liver cells (percentage of nuclear positive cells) in the endotoxemia groups was significantly higher than that in the normal control group (P0.05). TNF-α and IL-6 levels in liver tissue homogenates in the endotoxemia groups were significantly higher than those in the normal control group 6 and 12 hrs after LPS injection (P0.05).Endotoxemia can cause liver injury, resulting in liver cell damage and changes in liver function. NF-κB activation is involved in endotoxemic liver injury which may be mediated by inflammatory cytokines TNF-α and IL-6 synthesis.

To investigate the relationship of the promoter of matrix metalloproteinase-9 (MMP-9) gene polymorphisms with the susceptibility and clinical features of Helicobacter pylori (H. pylori)-related chronic gastritis and duodenal ulcer in children.One hundred children with chronic gastritis, 32 children with duodenal ulcer and 102 healthy children were enrolled.The promoter of MMP-9-1562C/T gene polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and sequencing. MMP-9 mRNA expression in gastric mucosa was confirmed by reverse transcription polymerase chain reaction.The genotype distributions and allele frequencies of MMP-9-1562C/T gene polymorphisms were similar in gastric upper gastrointestinal disease and healthy subjects. The relative risk for H.pylori infection in C/C genetype carriers was 3.1 times as high as that in T allele (C/T+T/T) carriers in children with chronic gastritis. MMP-9-1562 C/T gene polymorphisms did not affect MMP-9 mRNA expression level.These data suggest that MMP-9-1562 C/T gene polymorphisms are not associated with susceptibility to chronic gastritis and duodenal ulcer in children. The C/C genotype of MMP-9-1562 C/T gene polymorphism might be associated with H.pylori infection.

This study aimed to evaluate the genetic effect of the NR1H4 gene in the pathogenesis of idiopathic infantile cholestasis of Chinese subjects in Guangxi, China.Seventy-eight patients with idiopathic infantile cholestasis served as a study group and 95 infants without cholestasis as controls. Genomic DNA was extracted from peripheral venous blood leucocytes by phenol chloroform procedures. Polymerase chain reaction (PCR) was used to amplify all coded exons of NR1H4, and single-strand conformation polymorphism (SSCP) was used to analyze all amplification fragments. The PCR products with abnormal bands in SSCP were sequenced using an ABI 3100 sequencer.A novel heterozygous termination codon mutation in NR1H4 exon 5 (NR1H4 R176X, CGA-TGA) was found in one of the 78 patients. The patient with mutation R176X had high levels of bilirubin, alanine aminotransferase, γ-glutamyltransferase, cirrhosis and ascites despite biliary tract flushing procedures and drug therapy. In the other patients and controls, no mutation was detected.Heterozygous termination codon mutation of NR1H4 R176X was found in idiopathic infantile cholestasis. The novel mutation is useful to establish particular characteristics for differential diagnosis of idiopathic infantile cholestasis and to determine the influence of such gene defects in the prognosis.

AIM To evaluate the role of genetic factors in the pathogenesis of idiopathic infant cholestasis. METHODS We performed a case-control study, including 78 infants with idiopathic infant cholestasis and 113 healthy infants as controls. Genomic DNA was extracted from peripheral venous blood leukocytes using phenol chloroform methodology. Polymerase chain reaction was used to amplify the multidrug resistance protein 3 (MDR3) R652G fragment, and products were sequenced using the ABI 3100 Sequencer. RESULTS The R652G single nucleotide polymorphism (SNP) was significantly more frequent in healthy infants (allele frequency 8.0%) than in patients (allele frequency 2.60%) (P < 0.05), odds ratio, 0.29; 95% confidence interval, 0.12-0.84. The conjugated bilirubin in patients with the AG genotype was significantly lower than in those with the AA genotype (44.70 +/- 6.15 micromol/L vs 95.52 +/- 5.93 micromol/L, P < 0.05). CONCLUSION MDR3 R652G is negatively correlated with idiopathic infant cholestasis. Children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis.

To compare the prevalence of Helicobacter pylori (Hp) infection in children of Zhuang and Mulan ethnic groups, Guangxi Luocheng county, China and in children of Jing ethnic group, Central Vietnam and to analyze the association of HLA-DQA1 alleles of these ethnic groups' children with Hp infection.Serodiagnosis by determining Hp antibody with ELISA and determination of serum CagA, VacA and urease antibodies by immunoblotting were performed for 54 Zhuang, 76 Mulan and 109 Jing children. Polymerase chain reaction-single strand polymorphism (PCR-SSP) technique was applied to determine the polymorphism of the HLA-DQA1 locus of these children and then the association of HLA-DQA1 alleles of these minority children with Hp infection was analyzed by SAS software.The prevalence of Hp infection were 39% in Vietnamese Jing nationality, which was significantly lower than that in children of Guangxi Luocheng county (65% in Zhuang nationality and 58% in Mulan nationality) (P0.01). The distribution of HLA-DQA1 locus was not significantly different among the 3 groups. The frequency of HLA-DQA1 * 0104 allele was significantly higher in children with Hp infection than in children without Hp infection in each of the 3 groups (P0.01).The results indicated that the prevalence of Hp infection in Zhuang and Mulan minority ethnic groups in Guangxi, China was higher than that in Vietnamese Jing ethnic group children. HLA-DQA1 * 0104 allele may be associated with susceptibility to Hp infection.

To study the transformation of T lymphocyte subsets in children with Heliobacter pylori (H pylori) infection.The H pylori infection status were determined by a combination of ELISA and Western blot (immunoblot) technique in 98 children and T lymphocyte subsets in peripheral blood were determined by flow cytometrical analysis.There were 75 children positive with H pylori infection and 23 negative in 98 children. Comparing the proportion of peripheral blood T lymphocytic subsets in children with H pylori infection and without H pylori infection, it was found that a higher proportion of CD4 T-cells in infected children (39.02+/-7.71 vs 34.25+/-10.73, t = 2.246,P0.05) and higher value of CD4 to CD8 T-cells ratio (1.51+/-0.52 vs 1.25, t = 2.104, P0.05) were present, but there were not significant differences in CD3 T-cells and CD8 T-cells (73.11+/-10.02 vs 69.49+/-17.08, 27.22+/-6.07 vs 28.27+/-8.67, P0.05).Th1 cell-mediated immune responses may be induced by H pylori infection in children.