[Clinical characteristics of Wilson's disease with onset of acute liver failure in 19 children].

Objective: To analyze the clinical characteristics of Wilson's disease (WD) with onset of acute liver failure (ALF) in children. Methods: Clinical data of 19 children diagnosed with WD presented with ALF in Xi'an Children's Hospital from January 2016 to April 2021 were retrospectively analyzed, including general condition, clinical manifestation, laboratory examination, and gene detection. The children were divided into the death group and survival group according to the clinical outcome. The children who had hepatic WD with non-ALF onset during the same period were selected as the control. The general conditions and laboratory indexes were compared between death group and survival group, ALF group and non-ALF group. T-test, Mann Whitney U test or χ2 test were used to compare the differences between the two groups. Results: Of the 19 WD children with ALF onset, 10 were females and 9 were males. The age of admission was (10.1±2.6) years and time to onset of first visit was 9 (4, 15) days. Among the WD children with ALF onset, 4 children were lost to follow-up, 5 cases death (death group) and 10 cases survived (survival group). The ceruloplasmin in the death group was higher than that in the survival group (0.078 (0.055, 0.105) vs. 0.033 (0.027, 0.058) g/L, Z=-2.33, P=0.020). There were 95 children who had hepatic WD with non-ALF onset. The WD patients with ALF onset were older at admission (9.9 (8.0, 11.1) vs. 5.4 (3.7, 6.9) years, Z=-5.25, P<0.001), had higher ceruloplasmin (0.060 (0.030, 0.078) vs. 0.024 (0.006, 0.060) g/L, Z=-3.11, P=0.002), 24 h urinary copper (674 (205, 1 803) vs. 149 (108, 206) µg, Z=-4.25, P<0.001), and positive rate of K-F ring [17/19 vs. 7%(7/95), χ2=50.17, P<0.001] while shorter onset time at initial visit (0.3 (0.1, 0.5) vs. 1.0 (0.7, 6.0) months, Z=-4.28, P<0.001). There was no gender difference between the two groups [9/19 vs. 61%(58/95), χ2=1.22, P=0.269]. Of the 19 WD children with ALF onset, 13 had the ATP7B gene tested, and 15 reported variants were detected. The main variations were c.2333G>T (p. Arg778Leu), c.2621C>T (p. Ala874Val) and c.2975C>T (p. Pro992Leu). The allele frequencies were 6/26(23%), 4/26(15%) and 3/26(12%), respectively. Conclusions: Children of WD onset with ALF are school-aged and above. They have an acute onset, a short course of the disease, and poor prognosis. The positive rate of K-F ring, ceruloplasmin and urinary copper are higher than those of the hepatic WD children with non-ALF onset.

Effect of increased levels of adiponectin by administration of the adeno vector rAAV2/1-Acrp30 on glucose, lipid metabolism and ultrastructure of the aorta in Goto-Kakizaki rats with arteriosclerosis.

BACKGROUND: We used recombinant adeno-associated virus vector of adiponectin (AAV2/1-Acrp30) to study the effects of increased levels of adioponectin (by the administration of rAAV2/1-Acrp30) on arteriosclerosis, glucose and lipid metabolism in Goto-Kakizaki (GK) rats with arteriosclerosis. METHODS: Thirty GK rats with arteriosclerosis were divided into 3 equal groups: control group 1, control group 2 and the rAAV2/1-Acrp30-administered group. Saline, virus vector or rAAV2/1-Acrp30 (10 12 ng/ml) vector genomes administered to the rats in the corresponding group by intramuscular injection to the posterior limb by single administration, respectively. After 8 weeks, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum insulin, serum total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured in each group, and the ultrastructure of the aorta was seen by light and electron microscopy. RESULTS: Compared with control groups 1 and 2, in the rAAV2/1-Acrp30 group, there was a decrease in urine volume, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated haemoglobin, serum total cholesterol, triglycerides and low-density lipoprotein, and an increase in body weight and high-density lipoprotein (p< 0.05), while the level of serum insulin was not changed (p>0.05). Ultrastructure studies of the aorta showed that aortosclerosis in the rAAV2/1-Acrp30-administered group was less, and fewer lipid droplet vacuoles were seen in the vascular endothelial cytoplasm. Also various cell organelles and internal elastic lamina were seen, and there was no formation of lipid droplet and foam cells in the cytoplasm of the media of the smooth muscle. CONCLUSION: Adiponectin could improve blood glucose and lipid parameters and decrease atherosclerosis in the aorta of GK rats.