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.

Efficacy and safety of recombinant human growth hormone solution in children with growth hormone deficiency in China: a multicenter trial / 中华儿科杂志

<p><b>OBJECTIVE</b>Human growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.</p><p><b>METHODS</b>A 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.</p><p><b>RESULTS</b>After 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.</p><p><b>CONCLUSIONS</b>rhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.</p>

Blood glucose profile in children and adolescents in Beijing area / 中华儿科杂志

<p><b>OBJECTIVE</b>There are scant data about normal reference values of blood glucose (BG) in children. This study was conducted to learn the BG profile of children and adolescents in Beijing area.</p><p><b>METHOD</b>The population for survey was selected as a stratified cluster sample from 8 urban and 10 rural areas in Beijing. Fasting capillary blood glucose (FCBG) was determined in 19,593 children and adolescents aged 6 to 18 years in 4 urban and 3 rural areas using haemosaccharometer model II [Roche Diagnostic, (Shanghai) Ltd].</p><p><b>RESULTS</b>There were 1 9112 (97.5%) individuals with complete records, the mean age was 12.1 +/- 3.3 years (ranged from 6 to 18.9 years); 9514 (49.8%) were boys, 9598 (50.2%) were girls, 9792 were (51.2%) from urban areas and 9320 (48.8%) from rural areas. The average level of FCBG in boys was higher than that in girls (4.7 +/- 0.5 vs. 4.5 +/- 0.5, u = 28.0, P < 0.01). Among urban children, the trend of variation of FCBG was similar between boys and girls, the levels of FCBG increased with age, the peak of FCBG was reached at 12-13 years in urban girls, and from the age of 15 years, the level of FCBG declined. In boys, the FCBG level increased slowly from 13 years of age, there was no significant variation until 17 years old, and declined at the age of 18. Among suburban children, the trend of variation of FCBG was similar between boys and girls, both of them had two peaks, from 6 to 11 years old, FCBG of both boys and girls increased with age, and both reached the first peak at the age of 11 years. While at 13 years of age, there was an obvious drop in FCBG level. From 14 years of age on, there was a rise of FCBG in both boys and girls, and the second peak of FCBG was reached at 15 and 16 years of age in girls and boys respectively. The FCBG level of urban children was higher than that of rural children (4.7 +/- 0.5 vs. 4.6 +/- 0.5, u = 13.8, P < 0.01). The level of FCBG in overweight and obese children was higher than that of normal children. More boys, more obese and more urban children had abnormal FCBG.</p><p><b>CONCLUSIONS</b>The blood glucose level of children was associated with age, gender, obesity and district.</p>

Clinical Analysis of Gitelman Syndrome in Children / 实用儿科临床杂志

Objective To explore the clinical characteristics of Gitelman syndrome in children and the difference between Gitelman syndrome and Bartter syndrome.Methods Clinical date,biochemical tests and therapy of 6 patients diagnosed as Gitelman syndrome in Beijing children′s hospital from Mar.to Dec.2006 were retrospectively analyzed.At the same time,the relative articies of Gitelman syndrome and Bartter syndrome were reviewed.Results The symptoms of 6 patients appeared early.The age of onset of Gitelman syndrome at infancy stage,the main complains were growth delay,weakness,tetany.All patients had normal blood pressure.The biochemical tests showed hypocalemic,hypomagnesium,alkalosis and hyperreninemia.But the concentration of aldosterone was normal or little higher.The manifestations of all patients were relieved after taking both potassium and magnesium.Conclusion Gitelman syndrom and Bartter syndrome have differences at clinical syndrome and machanism of onset.

Survey of type 1 diabetes incidence in children from 1997 to 2000 in Beijing area / 中华儿科杂志

<p><b>OBJECTIVE</b>The incidence of type 1 diabetes varied in different countries, different nations and different regions. This survey was conducted to clarify the incidence of type 1 diabetes of children in Beijing area between 1997 and 2000, to compare and analyze the difference in incidence of type 1 diabetes between the 2 periods of 1988 - 1996 and 1997 - 2000.</p><p><b>METHOD</b>According to the criteria of WHO Diabetes Mondial (DIAMOND), data were collected from all the children younger than 15 years of age in Beijing area who had the onset of type 1 diabetes during Jan. 1st, 1997 to Dec. 31st, 2000. Using the capture-recapture methods, 95% confidence intervals of incidence were calculated with Poisson's distribution formula. The significance of differences was tested with Chi-square method.</p><p><b>RESULTS</b>The incidences of type 1 diabetes during 1997 - 2000 were around 0.76/100 000 to 1.21/100 000. The average yearly incidence was 1.014/100 000 (95% confidence interval was 0.98/100 000 - 1.16/100 000). There was no significant difference in the incidence between 1988 - 1996 and 1997 - 2000, and it showed the same result when the incidences were adjusted by age according to the Chinese population census in 2000 (The incidence was 0.83/100 000 in 1988 - 1996 and 0.86/100 000 in 1997 - 2000, respectively). The incidence was higher in 10 - 14 year-old group than the younger groups (P = 0.002). There was no significant difference between male and female groups, either.</p><p><b>CONCLUSIONS</b>No significant difference was found between the periods 1988 - 1996 and 1997 - 2000 when the average yearly incidence of type 1 diabetes of children in Beijing was compared. These results were different from the other countries' reports that the incidence of type 1 diabetes was increasing by 3% - 5% per annum. There was no significant difference between male and female groups either and there was a higher incidence of type 1 diabetes in 10 - 14 yr group than the other groups in 1997 - 2000. Although the life-style of Beijing people changed a lot, it didn't affect the incidence of type 1 diabetes in children in this area. But since many people migrated to Beijing from other parts of the country, the changes in constitutive proportions of population might have some impacts on the results of the survey.</p>

Ultrastructural characteristics of SARS associated virus in infected cells / 中华病理学杂志

<p><b>OBJECTIVE</b>Electron microscopical study of infected cells to identify the pathogenic agent of SARS.</p><p><b>METHODS</b>Vero E6 cells infected with lung autopsy samples or nasopharyngeal swabs from SARS patients of Beijing and Guangzhou were inoculated. The supernatant and cultured cells exhibiting identifiable cytopathic effect (CPE) were prepared for electron microscopic study.</p><p><b>RESULTS</b>Examination of CPE cells on thin-section revealed characteristic coronavirus particles within the cisternae of endoplasmic reticulum, Golgi apparatus, vesicles and extracellular space. They were mainly spherical or oval in shape, annular or dense, about 80 nm in diameter. Negative-stain electron microscopy identified coronavirus particles in culture supernatant, 80 - 120 nm in diameter, with club-shaped surface projections. Elongated, rod-, kidney- or other irregular shaped virons with the size of 100 - 200 nm by 60 - 90 nm were also found in the cultured cells infected with the lung samples from the Guangdong patients. Infectious virons entered cells by endocytosis or membrane fusion and released through a budding process.</p><p><b>CONCLUSION</b>These data indicate a novel coronavirus as the causative agent of SARS. Most viral particles showed typical characteristics of coronavirus. The potential role of special shape viruses is expected to be further investigated.</p>