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Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Guangdong, China. The purpose of this study was to explore the characteristics of newly diagnosed type 1 diabetes (T1D) patients with G6PD deficiency in a cohort of Chinese children and to investigate the relationship between the diabetic ketoacidosis (DKA) and hemolysis due to G6PD deficiency in these patients. Methods A total of 503 newly diagnosed T1D children aged 6 months–18 years were collected and their G6PD enzyme activity were measured. Fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and G6PD gene were analysed. The pH, HCO3, and plasma osmotic pressure between DKA patients with and without hemolysis at the presentation were compared. Results In the present study, G6PD deficiency accounted for 5.3% of newly diagnosed T1D children. There were no significant differences in FPG/HbA1c and HbA1c levels between T1D children alone and T1D children with G6PD deficiency. Hemolysis appeared in five of the twenty-two DKA patients with G6PD deficiency. Two patients had fever at onset and were given ibuprofen and cefazolin. The other three patients did not have infection or ingestion of hemolytic drugs. There were no significant difference in pH, HCO3, and osmotic pressure between the children with DKA with and without hemolysis at the presentation. The hemolysis occurred between 2 and 7 days after admission and the hyperglycaemia had been corrected by the time hemolysis occurs. Four G6PD gene mutations were found in the diabetes with G6PD deficiency patients: c.1376G > T, c.1388G > A, c.95A > G, and c.871G > A, all of which were genes with high frequency of G6PD deficiency in Guangdong Province. No correlation between genotype and hemolysis was found. Conclusion In the present study, we found the frequency of G6PD deficiency among newly diagnosed T1D children was similar to that of the general population. However, DKA children with G6PD deficiency are prone to occur hemolytic anemia, and these hemolysis usually occurs when DKA is corrected and blood glucose is in homeostatic state, which is easy to be ignored. To reduce the risk of this complication, especially in areas with high incidence of G6PD deficiency, screening for G6PD activity in people with newly diagnosed diabetes should be considered.

Background: Serum HBV RNA level has the potential to monitor antiviral therapy in patients with chronic hepatitis B. This study aimed to explore serum HBV RNA dynamic change pattern and its predict value on the efficacy of 96 weeks nucleos(t)ide analogue (NA) treatment in HBeAg-positive and HBeAg-negative patients with chronic hepatitis B (CHB).Methods: A real-life cohort study of 78 patients with CHB on NA treatment was conducted. Dynamic change patterns of serum HBV RNA and correlation with other HBV markers in the early treatment period of 96 weeks of NA treatment in patients with CHB were determined and compared. The performance of serum HBV RNA on treatment efficacy was analyzed by receiver operating characteristic (ROC) analyses. Results: HBeAg-positive and HBeAg-negative patients with CHB had similar viral change patterns during NA treatment. Serum HBV RNA level was consistently correlated with HBeAg and HBsAg titers in HBeAg-positive patients during NA treatment, but serum HBV RNA was only moderately correlated with serum HBV DNA level in HbeAg-negative patients before treatment. Serum HBV RNA decreased more rapidly in patients with the HBeAg seroconversion (SC) response than in patients without the HBeAg SC response; it had good early discriminatory ability for the HBeAg response with area under the ROC curve (AUROC) of 0.70 and 0.730 at 12 and 24 weeks of treatment, respectively. The cutoff value of serum HBV RNA of 4.31 log cps/mL in combination with the HBeAg decrease degree of 1.55 at 24 weeks of treatment had a good two-way predictive capability for the HBeAg response (PPV%: 83.33% and NPV%: 81.25%), and the specificity was 96.30%. Conclusion: Serum HBV RNA level had early discriminatory ability for the HBeAg response. Early HBeAg response can improve the discriminatory ability of serum HBV RNA.

Background Sulfonylurea therapy can improve glycemic control and ameliorate neurodevelopmental outcomes in patients suffering from neonatal diabetes mellitus (NDM) with KCNJ11 or ABCC8 mutations. As genetic testing results are often delayed, it remains controversial whether sulfonylurea treatment should be attempted immediately at diagnosis or doctors should await genetic confirmation. Objective This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available. Methods The medical records of NDM patients with their follow-up details were reviewed and molecular genetic analysis was performed. Sulfonylurea transfer regimens were applied in patients diagnosed after May 2010, and glycemic status and side effects were evaluated in each patient. Results There were 23 NDM patients from 22 unrelated families, 10 had KCNJ11 mutations, 3 harbored ABCC8 mutations, 1 had INS mutations, 4 had chromosome 6q24 abnormalities, 1 had a deletion at chromosome 1p36.23p36.12, and 4 had no genetic abnormality identified. Sixteen NDM infants were treated with glyburide at an average age of 49 days (range 14-120 days) before genetic confirmation. A total of 11 of 16 (69%) were able to successfully switch to glyburide with a more stable glucose profile. The responsive glyburide dose was 0.51 ± 0.16 mg/kg/d (0.3-0.8 mg/kg/d), while the maintenance dose was 0.30 ± 0.07 mg/kg/d (0.2-0.4 mg/kg/d). No serious adverse events were reported. Conclusions Molecular genetic diagnosis is recommended in all patients with NDM. However, if genetic testing results are delayed, sulfonylurea therapy should be considered before such results are received, even in infants with newly diagnosed NDM.

Objective To explore the clinical presentation and molecular genetic characteristics of a cohort of congenital hyperinsulinism (CHI) patients from southern China and also to explore the most appropriate therapeutic approaches. Methods We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was performed for KCNJ11 and ABCC8 genes. The GLUD1 gene was sequenced in patients with hyperammonaemia. GCK gene sequencing was performed in those patients with no mutation identified in the ABCC8, KCNJ11 or GLUD1 genes. Results ABCC8 mutations were identified in 16 (25%) of the cohort, GLUD1 mutations were identified in five children, and no KCNJ11 or GCK mutations were identified. Moreover, some unique features of ABCC8 gene mutations in southern Chinese CHI patients were found in this study. The most common mutation was a deletion/insertion mutation p.Thr1042GlnfsX75 was found in five unrelated patients, which possibly represents a relatively common mutation in southern China. Five novel ABCC8 mutations were detected. The mutations were p.Phe5SerfsX72, p.Gln273ArgfsX85, p.Leu724del, p.Asp1447Gly and IVS 25-1G>T. Five compound heterozygous mutations of ABCC8 gene were identified in this study, and three of these patients were diazoxide-responsive. Forty patients were diazoxide-responsive, 13 patients were diazoxide-unresponsive and 12 patients received dietary treatment only. A pancreatectomy was performed in 10 patients who were unresponsive to medical treatment. Conclusion To the best of our knowledge, this is the first study of CHI in south China. Mutations in ABCC8 are the most common causes of CHI in this cohort. Diazoxide and dietary treatment were effective in most patients. Multicentre studies are necessary to obtain the long-term follow-up characteristics of such patients at a national level.

Objective The purpose of this study was to investigate the molecular basis of maturity-onset diabetes of the young (MODY) by whole-exome sequencing (WES) and estimate the frequency and describe the clinical characteristics of MODY in southern China. Methods Genetic analysis was performed in 42 patients with MODY aged 1 month to 18 years among a cohort of 759 patients with diabetes, identified with the following four clinical criteria: age of diagnosis ≤18 years; negative pancreatic autoantibodies; family history of diabetes; or persistently detectable C-peptide; or diabetes associated with extrapancreatic features. GCK gene mutations were first screened by Sanger sequencing. GCK mutation-negative patients were further analyzed by WES. Results Mutations were identified in 24 patients: 20 mutations in GCK, 1 in HNF4A, 1 in INS, 1 in ABCC8, and a 17q12 microdeletion. Four previously unpublished novel GCK mutations: c.1108G>C in exon 9, and c.1339C>T, c.1288_1290delCTG, and c.1340_1343delGGGGinsCTGGTCT in exon 10 were detected. WES identified a novel missense mutation c.311A>G in exon 3 in the INS gene, and copy number variation analysis detected a 1.4 Mb microdeletion in the long arm of the chromosome 17q12 region. Compared with mutation-negative subjects, the mutation-positive subjects had lower hemoglobin A1c and initial blood glucose levels. Conclusions Most MODY cases in this study were due to GCK mutations, which is in contrast to previous reports in Chinese patients. Diabetes associated with extrapancreatic features should be a clinical criterion for MODY genetic analysis. Mutational analysis by WES provided a precise diagnosis of MODY subtypes. Moreover, WES can be useful for detecting large deletions in coding regions in addition to point mutations.

Background There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY. Methods Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children’s hospital in South China. Clinical data were obtained from medical records. Blood was collected from the patients and their parents for glucokinase (GCK) gene analysis. Parents without diabetes were tested for fasting glucose and HbA1c. Clinical information and blood for GCK gene analysis were obtained from grandparents with diabetes. GCK gene mutational analysis was performed by polymerase chain reaction and direct sequencing. Patients without a GCK gene mutation were screened by targeted next-generation sequencing (NGS) technology for other MODY genes. Results Nine children tested positive for GCK gene mutations while two were negative. The nine GCK-MODY patients were from unrelated families, aged 1 month to 9 years and 1 month at first detection of hyperglycaemia. Fasting glucose was elevated (6.1–8.5 mmol/L), HbA1c 5.2–6.7% (33.3–49.7 mmol/mol), both remained stable on follow-up over 9 months to 5 years. Five detected mutations had been previously reported: p.Val182Met, c.679 + 1G > A, p.Gly295Ser, p.Arg191Gln and p.Met41Thr. Four mutations were novel: c.483 + 2 T > A, p.Ser151del, p.Met57GlyfsX29 and p.Val374_Ala377del. No mutations were identified in the other two patients, who were also tested by NGS. Conclusions GCK gene mutations are detected in Chinese children and their family members with typical clinical features of GCK-MODY. Four novel mutations are detected.

The aim of this study was to investigate the effectiveness of a high-dose zinc sulfate and low-dose D-penicillamine combination in the treatment of pediatric Wilson's disease (WD). A retropective chart review of 65 patients with WD was conducted. These patients received D-penicillamine (8-10 mg/kg/day) and zinc sulfate as the primary treatment. The pediatric dose of elemental zinc is 68-85 mg/day until 6 years of age, 85-136 mg/day until 8 years of age, 136-170 mg/day until 10 years of age and then 170 mg/day, in 3 divided doses 1 h before meals. After clinical and biochemical improvement or stabilization, zinc sulfate alone was administered as the maintenance therapy. Under treatment, the majority of patients (89.2%) had a favourable outcome and 3 patients succumbed due to poor therapy compliance. No penicillamine-induced neurological deterioration was noted and side-effects were observed in

Type 1 diabetes is an autoimmune disorder, which occurs due to β cell damage. Interleukin (IL)-10, a pleotropic cytokine, has been reported to have anti‑inflammatory, immunosuppressive and immunostimulatory properties. Administration of IL‑10 is known to prevent autoimmune diabetes in non‑obese diabetic (NOD) mice. However, the mechanism of IL‑10‑induced protection in NOD mice requires further investigation. The aim of the present study was to evaluate the protective effect of transgenic IL‑10 expression in pancreatic β cells against autoimmune damage in NOD mice and to elucidate its mechanism of action. Female NOD mice (9 weeks old) were intraperitoneally injected with an adenovirus carrying either IL‑10 (Adv‑IL‑10) or green fluorescent protein (Adv‑GFP). Blood glucose was monitored weekly and the expression of IL‑10 was evaluated using reverse transcription quantitative polymerase chain reaction. IL‑10 and interferon (IFN)‑γ expression levels in serum and splenocytes were analyzed. CD4+CD25+FoxP3+ T regulatory (Treg) cells were determined by flow cytometry. Apoptosis of pancreatic β cells was determined using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick‑end labeling assay and expression levels of Fas and caspase‑3 were estimated by immunohistochemistry analysis. The results revealed that mice treated with IL‑10 showed less severe insulitis and a lower incidence of diabetes compared with the saline control and Adv‑GFP groups. In addition, compared with the control group, IFN‑γ levels were decreased in sera and splenocytes, while IL‑10 expression was increased in sera only. The number of CD4+CD25+FoxP3+ Treg cells was increased in IL‑10‑injected mice. Furthermore, the expression levels of Fas and caspase‑3 were decreased in IL‑10‑injected mice compared with that of GFP‑injected and control mice, which was concomitant with a reduction in β cell apoptosis. In conclusion, the present study demonstrated that IL‑10 gene transfer reduced the expression of the inflammatory cytokines, attenuated pancreatic insulitis and inhibited β cell apoptosis. This therefore indicated that IL-10 reduced the incidence of diabetes in female NOD mice.

We present eight cases with short stature, pituitary hyperplasia, and hypothyroidism. Pituitary hyperplasia due to primary hypothyroidism was diagnosed on the basis of clinical manifestations, endocrine examination and MRI. After 2 to 6 months of L-thyroxine replacement therapy, the signs of hypothyroidism disappeared; free triiodothyronine, free thyroxine, thyrotropin and prolactin became normal; and pituitary enlargement regressed. In two children, the growth rate remained low when treated with L-thyroxine, but with additional recombinant human growth hormone (rhGH), the height increased by 11 cm per year. No recurrence of lesions was found on follow-up.