Objective:To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD).Methods:Two children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively.Results:Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutacoic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c. 722C>T variants of the HMGCL gene, which was rated as uncertain significance(PM2_Supporting+ PP3). Child 2 was found to harbor homozygous c. 121C>T variants of the HMGCL gene, which was rated as pathogenic(PVS1+ PM2_Supporting+ PP4). Conclusion:Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may can facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.

Objective:The clinical and molecular genetic characteristics of 46, XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. Methods:The clinical data of children with NR5A1 gene variants diagnosed at the Children′s Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. Results:At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1~9), including micropenis (100.0%), hypospadia (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomol karyotypes were 46, XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. Conclusion:The clinical phenotype of 46, XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.

Objective:To analyze clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH) in children.Methods:Clinical data of 0-18 year old CHH patients diagnosed in the Department of Endocrinology, Genetics and Metabolism of Children′s Hospital Affiliated to Zhengzhou University from January 1, 2016 to December 31, 2023 were retrospectively analyzed, including their hormone levels and genetic test results.Results:A total of 95 patients with CHH were included. Among them, 25 were diagnosed before the age of 3, 37 between the ages of 3-14, and 33 were over 14 years old at the time of first diagnosis. The primary manifestations were micropenis(95 cases, 100%) and cryptorchidism(46 cases, 48.5%). The incidence of cryptorchidism was the lowest in the group over 14 years of age. Hormonal analysis revealed that the peak levels of LH following statin B and GnRH stimulation, the peak levels of FSH after GnRH stimulation, and testosterone levels following hCG stimulation were the highest in the infant group. Genetic analysis identified 20 CHH-related genes in 61 out of 77 cases.Double-gene mutation accounted for 7.8%(6/77) and triple-gene mutation accounted for 3.9%(3/77). The most common mutations were FGFR1(18/77, 23.4%), CHD7(12/77, 15.6%), PROKR2(11/77, 14.3%) and ANOS1(6/77, 7.8%). The incidence of cryptorchidism in these four genotypes was 50%, 75%, 45.5% and 83.3%, respectively. The incidence of testicular dysfunction was 22.2%, 16.7%, 27.3%, and 16.7%, respectively, with no statistical significance.Conclusion:The primary manifestation of CHH is micropenis and cryptorchidism. In children with CHH, the incidence of testicular Leydig cell and Sertoli cell dysfunction increased with age in CHH children. FGFR1, CHD7, PROKR2 and ANOS1 were common variants of CHH.

OBJECTIVE: To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature. METHODS: Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software. RESULTS: The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4). CONCLUSION The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.
Alkaline Phosphatase ; Child ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypophosphatasia/genetics* ; Mutation ; Whole Exome Sequencing

Objective:To evaluate the effectiveness of exogenous melatonin in preventing delirium in critically ill patients.Methods:The computer searched Pubmed, Medline, Embase, Web of Science, the Cochrane Library and other English databases for randomized controlled trials on the efficacy of exogenous melatonin in the prevention of delirium in critically ill patients. The retrieval time was from the establishment of the database to March 2021. Two researchers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Revman 5.3 software was used for meta-analysis.Results:A total of 10 randomized controlled trials and 1 224 critically ill patients were included. The results of meta-analysis showed that there were no significant differences in the incidence of delirium during hospitalization (relative risk [ RR] 0.72, 95% confidence interval [ CI] 0.47-1.09; Z=1.57, P=0.12), ICU hospitalization time (mean difference [ MD] -0.36, 95% CI -1.01-0.28; Z=1.11, P=0.27), mechanical ventilation time ( MD -49.42, 95% CI -126.63-27.80; Z=1.25, P=0.21) and mortality ( RR 0.74, 95% CI 0.42-1.30; Z=1.05, P=0.29) between the experimental group and the control group. Conclusion:Exogenous melatonin can not prevent the occurrence of delirium in critically ill patients, nor can it shorten the hospitalization time and mechanical ventilation time in intensive care unit and reduce the mortality.

This paper aims to push health scientific popular knowledge and carry out targeted patient health education for certain patients, based on the demand of health education for specific diseases and population. Taking the female climacteric health scientific popularization as an example, the authors summarized the practice of popularizing scientific education in a tertiary specialized hospital based on the cognitive level and health education needs of outpatients and the general public. A multidisciplinary health scientific popularization team was set up to communicate popular science knowledge to patients and other menopausal women in need through multi-channel and multi-platform forms. Such means include online ones, offline ones, and cooperation with various social organizations. The implementation of health scientific popularization mode meets the needs of patients and the general public. The implementation of this mode of health popularization could improve their self-health management ability and health accomplishment. It provides a good reference for public hospitals to carry out health science popularization.

OBJECTIVE: To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity. METHODS: Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results. RESULTS: NGS has identified a novel heterozygous missense mutation (c.125A>C, p.Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation. CONCLUSION A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.
Brachydactyly ; complications ; DNA Mutational Analysis ; Humans ; Mutation ; Obesity ; complications ; Pedigree

Objective The present study aims to establish a professional knowledge structure for the family planning technical team at the current stage in Zhejiang Province so as to meet the needs of training and offer reference evidences for specific and effective training. Methods This study applied a stratified cluster sampling method to carry out a self-administered questionnaire which was anonymous and including general survey, the situation of training, as well as the professional skill structure. This questionnaire was designed through the method of literature review and based on the actual situation of the operation. It col-lected the information from 365 family planning technical staffs who were from different levels of plan family service agencies in four cities, which were Hangzhou, Jiaxing, Taizhou, Wenzhou, respectively, from April to June in 2016. Epidata 3.0 software was utilized to record the data and the data was analyzed using SPSS version 20.0. Subsequently, the relationship between the mastery of professional skill and demographic characteristics was researched by students' t test and one-way analysis of variance (ANOVA) test. Results The education background, major and the professional title structure of the family planning technical staffs varied among different areas. At present, it seems that most of the family planning technical staffs have an aspiration to attend training and 97.53% of them wanted to get professional knowledge through training. The result was not satisfactory when surveyed 298 staff for the mastery of knowledge and skills: 3.66% (9/246) for pelvic floor rehabilitation training, 7.42% (19/256) for genetic counseling, 4.9% (12/245) for prena-tal screening, 5.26% (13/247) for screening and prevention of common breast diseases and 6.22% (15/241) for infertility treatment. There was a significant difference (P=0.000) among the different levels of plan family service agency, education background, major, occupation type and professional title in the mastery of professional knowledge and skill. Conclusion It is necessary to improve the training plan and conduct clas-sification and layering training since the knowledge and skills of family planning technical personnel can not meet the needs of reproductive health services at the new period.

Gitelman's syndrome (GS) is an autosomal recessive hereditary tubulopathy.It is caused by sodium reabsorption in the distal convoluted tubule of the renal unit,which is not yet fully cured.It is characterized by great heterogeneity with clinical manifestations.Some patients with no symptoms,were confirmed by hypokalemia with physical examination.The others can be manifested as fatigue,nocturia,polydipsia and hypotension.Less literature is reported about GS combined with osteoarthrosis.In this report,the author reported a patient of GS with osteoarthrosis characterized by hypokalemia,hypomagnesemia,metabolic alkalosis,lower blood pressure,and swelling and pain in left knee joint.The symptoms were improved after treatment with potassium and magnesium supplementation

Objective To study the diagnostic significance and clinical value of genetic analysis in children with neonatal diabetes. Methods Gene mutation analysis was performed in four patients from Zhengzhou children ' s hospital with diagnosis of with neonatal diabetes. Therapeutic effect of glibenclamide in patients with or without gene mutation was compared. Results KCNJ11 gene mutation was found in two patients with neonatal diabetes. Glibenclamide was found only effective for blood glucose control in patients with KCNJ11 mutation. Therefore, Insulin remains the best therapeutic choice in patients without the genetic mutation. Conclusions Genetic mutation status may be useful in choosing treatment options of neonatal diabetic patients, therefore, should be performed in all children with neonatal diabetes.