Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature / 浙江大学学报·医学版

OBJECTIVE@#To assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature.@*METHODS@#One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group ( =108) and rhGH group ( =43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg ·d , and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored.@*RESULTS@#After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDS (height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group( < 0.05 or < 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose.@*CONCLUSIONS@#AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in two cases / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report on two cases affected with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).</p><p><b>METHODS</b>Two unrelated Chinese infants affected with IPEX were investigated. Case 1 was a 4-month-old boy with neonatal diabetes and severe enteropathy. Case 2 was a 6-day newborn boy with neonatal diabetes and ketoacidosis. DNA samples of the two infants and their parents were sequenced for FOXP3 gene mutations. Suspected mutations were verified among 100 unrelated healthy controls. The function of mutations was predicted with bioinformatics software.</p><p><b>RESULTS</b>Both infants had onset of the disease during neonatal period, and manifested insulin-dependent diabetes mellitus, persistent diarrhea, eczema and malnutrition. In case 1, a novel splice site mutation was identified in intron 9 (c.967+3A>T) of the FOXP3 gene, for which his mother was a carrier. For case 2, a missense mutation (c.1150G>A) was detected in exon 11 of the FOXP3 gene, for which his mother was also a carrier. The IVS9 c.967+3A mutation was not detected among the 100 healthy controls. As predicted with Human Splicing Finder software, the c.967+3A>T mutation may influence the splicing of mRNA and affect the function of protein.</p><p><b>CONCLUSION</b>Both cases had typical clinical manifestation of the IPEX syndrome, among whom a novel splice site mutation (IVS9 c.967+3A>T) and a missense mutation (c.1150G>A) of the FOXP3 gene were identified. The clinical manifestation of the IPEX syndrome may be variable and the mortality is high. FOXP3 gene sequencing is recommended when insulin-dependent diabetes mellitus is diagnosed during the neonatal period.</p>

Mutation analysis of AAAS gene in a child with Allgrove syndrome / 中华内分泌代谢杂志

Objective To study the AAAS gene mutations in a child with autosomal recessive Allgrove syndrome. Methods Clinical data were collected and blood samples were obtained from the proband of Allgrove syndrome and her parents. Genomic DNA was extracted and sequenced by PCR amplification. Subclone sequencing was performed to validate the gene mutations. The disease-causing potentials of mutation genes were evaluated by the Mutation Taster, and the target protein tertiary structure was modelled by the Swiss Model. Results A new heterozygous insertion mutation(c. 1347_1348insG) of exon 15 in the proband was identified and firstly reported. Other two reported mutations were detected, which were the heterozygous mutation c. 688C>T in the patient and her mother, and the homozygous mutation c. 855C>T in the proband and her parents. In addition, it was confirmed that the novel compound heterozygous mutations(c. 688C>T, c. 1347_1348insG) in the AAAS gene of the proband were pathogenic mutation locus. Conclusion The heterozygous mutation(c. 1347_1348insG) of AAAS gene was firstly reported. In case of the patients being clinically misdiagnosed, related-gene detection should be performed for the patients who were diagnosed with primary adrenal insufficiency during the period of infants and young childhood.

Iodine 131 joint radio frequency ablation treatment for child with hyperthyroidism goiter: one case report / 浙江大学学报·医学版

A 12-year-old girl presented with a history of cervical mass, and one week of throat discomfort and dyspnea. Five years ago, the patient was diagnosed as Hashimoto's thyroiditis and hyperthyroidism; she received antithyroid drug treatment, but the result was not satisfactory. B-ultrasonic showed that the size of thyroid gland was 8.1 cm×3.2 cm in the left and 8.2 cm×4.8 cm in the right. After iodine 131 combined with radiofrequency ablation (RFA) treatment, throat discomfort and recumbent breathing difficulties disappeared, and B-ultrasonic showed that the size of thyroid reduced to 2.3 cm×1.7 cm (left) and 2.8 cm×2.0 cm (right). No recurrence was observed during the two and a half years of follow-up.

Association of PA X 4 R192S and R192H polymorphism with obesity in children and adolescents / 临床儿科杂志

Objective To investigate association of the paired box 4 (PA X 4) gene rs3824004 (574C>A; R192S) and rs2233580 (575G>A; R192H) polymorphism with obesity and metabolic markers in children and adolescents. Methods A total of 103 obese children were randomly selected, and an average age was (10.82±2.57) years, and body mass index (BMI) was (26.82±4.57) kg/m2. At the same period, 100 normal weight children were selected as the control group, and an average age of (10.60±2.84) years, and BMI was (16.79±2.13) kg/m2. The blood pressure, physical measurements, and blood metabolic parameters were measured and compared. The oral glucose tolerance test (OGTT) and insulin release test were performed in the obesity group. The homeostasis model insulin resistance index (HOMA-IR) and the overall insulin sensitivity index (WBISI) were calculated. PA X 4 rs3824004 and rs2233580 polymorphism were detected by PCR.The differences of allele frequency and genotype frequency of polymorphic loci were analyzed, and the correlation between different genotypes and metabolic indexes was analyzed. Results The height, weight, BMI, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, waist to height ratio (WHtR), fasting blood glucose (FPG), total cholesterol (TC), low density lipoprotein (LDL), triacylglycerol (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the obesity group were significantly higher than those in the control group, and the high density lipoprotein (HDL) was significantly lower than that in the control group (all P<0.05). The frequency of gene distribution was in accordance with the Hard-Weinberg balance. The frequencies of A allele of rs3824004 in obesity and control groups were 4.9% and 5.0%, respectively, and the frequencies of CA genotype were 9.7% and 10.0%, respectively, and there was no significant difference between two groups (P>0.05). The frequency of GA allele of rs2233580 in obesity group was 25.2%, which was significantly higher than that in control group (P<0.05). The BMI and waist in rs2233580 GA genotype were significantly higher than those in GG genotype (all P <0.05). However,logistic regression analysis showed that there was no correlation between PA X 4 rs2233580 genotype and metabolic markers (all P>0.05).There were no significantly differences in HOMA-IR and WBISI among different genotypes of PA X 4 rs2233580 in obesity group(all P>0.05).Conclusions PA X 4 rs2233580 affects children's BMI and waist circumference and may be involved in the development of childhood obesity, but it is not an independent risk factor for obesity in children and adolescents.

Comparison of clinical application of two definitions of metabolic syndrome in children and adolescents / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To compare and evaluate clinical applications of two definitions of metabolic syndrome in children and adolescents, which was developed by Pediatric Academy of Chinese Medical Association in 2012 (Chinese definition) and by International Diabetes Federation in 2007 (IDF definition), respectively.</p><p><b>METHODS</b>593 obese children and adolescents aged 10 ≊16 y from July 2006 to December 2012 were enrolled in the study. The diagnostic concordance of two definitions for metabolic syndrome and individual components was estimated, and their sensitivity and specificity for detecting insulin resistance and early macrovascular complications were compared.</p><p><b>RESULTS</b>The concordance between two definitions for diagnosing metabolic syndrome was good (kappa=0.626); as for detecting the individual components, the Kappa concordance index were 1.000, 0.803, 0.780, 0.734 and 0.594 for hypertriglyceridemia, hyperglycemia, cholesterol abnormality and hypertension, respectively. The incidence of insulin resistance and early macrovascular complications, detected by the two definitions, were both increased with increasing number of abnormal components. The sensitivity and specificity for detecting insulin resistance in children with metabolic syndrome were 54.5% and 65.7% by Chinese definition, and 36.1% and 83.1% by IDF definition; while the sensitivity and specificity for detecting early macrovascular complications were 58.3% and 55.8% by Chinese definition, and 37.3% and 70.8% by IDF definition. After adjusting for age and sex, compared to the obese children and adolescents without metabolic syndrome, the odds ratios of insulin resistance and early macrovascular complications were 2.166 (P<0.001) and 1.771(P=0.008) for children with metabolic syndrome diagnosed by Chinese definition, and the odds ratio of insulin resistance and early macrovascular complications were 2.618 (P<0.001) and 1.357 (P=0.190) by IDF definition.</p><p><b>CONCLUSION</b>The concordance between Chinese and IDF definitions for diagnosing metabolic syndrome in Chinese obese children and adolescents is good. Compared to IDF definition, Chinese definition is more sensitive for hypertension, hyperglycemia and hypercholesterolemia, thus it can more effectively detect insulin resistance and early macrovascular complication.</p>