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Floating-Harbor syndrome (FHS) is an autosomal dominant genetic disease caused by SRCAP mutation. This article reports the clinical features of a boy with FHS. The boy, aged 11 years and 7 months, attended the hospital due to short stature for more than 8 years and had the clinical manifestations of unusual facial features (triangularly shaped face, thin lips and long eyelashes), skeletal dysplasia (curvature finger), expressive language disorder, and retardation of bone age. Genetic detection revealed a novel heterozygous mutation, c.7330 C>T(p.R2444X), in the SRCAP gene. The boy was diagnosed with FHS based on these clinical manifestations and gene detection results. FHS is rare in clinical practice, which may lead to missed diagnosis and misdiagnosis, and gene detection may help with the clinical diagnosis of FHS in children.
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Criança , Humanos , Masculino , Anormalidades Múltiplas , Adenosina Trifosfatases , Anormalidades Craniofaciais , Transtornos do Crescimento , Comunicação InterventricularRESUMO
Objective To investigate the clinical features of these children with congenital hyperinsulinism (CHI) who had no response to diazoxide and provide a theoretical foundation for the formulation of CHI treatment strategy.Methods Eighteen patients with CHI who had no response to diazoxide hospitalized in Beijing Children's Hospital from 2008 to 2012 were chosen as research subjects.Their clinical data were analyzed retrospectively.Results There were 18 patients with persistent hypoglycemia after using diazoxide,which indicated that they had no response to diazoxide.Twelve patients of them were born as macrosomia and their onset age was less than 6 months.Half of the children(9/18 cases) even had hypoglycemia in neonatal period.All the manifestations were conformed to the clinical characteristics of ATP-sensitive potassium channel CHI.Four children who were unresponsive to diazoxide received octreotide treatment,and it was effective on them.Four patients had a near-total pancreatectomy.After a long-term followup study,their blood sugar maintained a normal level,and they did not appear serious postoperative complications.Conclusions Children with CHI who have no response to diazoxide are characterized by coming earlier and higher birth weight.Octreotide is proposed in case of non-response to diazoxide.When medical treatment is not efficient in prevention of hypoglycemia,a subtotal pancreatectomy has to be considered as a last resort.
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Objective To study the relationship between cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway and glutamine-stimulated insulin secretion.Methods In the prerequisite of the existence of glucose(0.25 mmol/L),the insulin secretion of βHC9 cells was stimulated with different concentrations of glutamine (0.0,0.5,1.0,2.0,5.0 mmol/L),then culture liquids were extracted and centrifugalized,and the insulin levels in the cell culture liquids and the cAMP levels in βHC9 cells were determined,so as to study the effects of glutamine stimulation on the insulin level in cell culture liquids and cAMP levels in βHC9 cells were assayed.Results In the prerequisite of the glucose existence,with the increasing of the concentrations of glutamine(0.0,0.5,1.0,2.0,5.0 mmol/L),the insulin levels[0.0 ng/(mL · million),19.1 ng/(mL · million),29.1 ng/(mL · million),30.1 ng/(mL · million),33.9 ng/(mL · million)] in cell culture liquids and the cAMP levels (0.0 pmol/million,40.0 pmol/million,51.5 pmol/million,52.5 pmol/million,61.3 pmoL/million) in βHC9 cells increased accordingly.Conclusion Glutamine has amplifying effect on glucose stimulated insulin secretion,such amplifying effect needs the existence of cAMP to be prerequisite.
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Objective To study the association of fat mass and obesity associated gene(FTO gene) and genetic onset mechanism of obesity in Chinese children.Methods Two hundred and one Chinese children with obesity in Beijing Children's Hospital Affiliated to Capital Medical University from Jan.to Sep.2010,were selected as research subjects,183 healthy adult blood donors were selected as normal controls.Mass Spectrometry techniques were used to study the distributions of the alleles and gene type of FTO in patients and controls.And the relationship between FTO gene polymorphism and obesity in Chinese children were studied.Results The distributions of 5 FTO gene polymorphisms (rs9939609A,rs8050136A,rs3751812T,rs1421085C,rs7193144C) in obesity patients and healthy controls had significant differences.And the Haplotype analysis showed that all of the single nucleotide polymorphisms(SNPs) were in linkage disequilibrium,and three out of six (CTGGTCTGG,TCTGCAAAA,CTGGCCTGG) had significant differences between obesity patients and healthy controls (P < 0.05).Conclusions The gene polymorphisms of rs9939609,rs8050136,rs3751812,rs1421085,rs7193144 of FTO gene confer significant susceptibility to obesity in Chinese children.The haplotypes of CTGGTCTGG,TCTGCAAAA,CTGGCCTGG have significant differences between obesity patients and healthy controls.
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Objective To reveal the clinical features of children with transient neonatal diabetes mellitus (TNDM) in order to provide a basis for the TNDM treatment strategy formulation.Methods Four patients diagnosed as TNDM hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University from Dec.2008 to Dec.2010 were chosen as research subjects.Their clinical data were analyzed retrospectively.Results The 4 patients diagnosed as TNDM started insulin therapy.Two cases of the 4 patients transferred from insulin to oral Sulfonylureas for 2-3 weeks after their conditions became steady.One patient was treated with Sulfonylureas successfully and the other one was partially effective with this therapy.After 2 to 3 years follow-up,3 cases remitted in 1 month after birth with no other severe complications,one case lost.Conclusions Infants with TNDM had unique clinical features.The patients develop diabetes in the first few weeks of life but go into remission in a few months.So the follow-up for those TNDM patient is very essential for clinical classification.Oral glibenclamide therapy seems highly effective and safe for some TNDM patients.
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<p><b>OBJECTIVE</b>To investigate the glutamate dehydrogenase 1 (GLUD1) gene mutation of three patients diagnosed as glutamate dehydrogenase congenital hyperinsulinism (GDH-HI).</p><p><b>METHODS</b>Three patients diagnosed as GDH-HI and their parents were involved in the study. PCR-DNA direct sequencing was used to analyze the exons 6,7,10,11 and 12 of the GLUD1 gene.</p><p><b>RESULTS</b>In the first case, an R269H heterozygous mutation was found in the GLUD1 gene, with autosomal dominant inheritance. In the second case, there was a de novo S445L heterozygous mutation of the GLUD1 gene. No mutation was detected in the third case.</p><p><b>CONCLUSION</b>In Chinese, R269H, S445L heterozygous mutation of the GLUD1 gene can lead to GDH-HI. Genetic analysis is necessary in making genetic diagnosis of congenital hyperinsulinsm.</p>
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Adulto , Feminino , Humanos , Lactente , Masculino , Povo Asiático , Genética , Sequência de Bases , China , Hiperinsulinismo Congênito , Genética , Análise Mutacional de DNA , Éxons , Desidrogenase de Glutamato (NADP+) , Genética , Dados de Sequência Molecular , Mutação de Sentido IncorretoRESUMO
<p><b>OBJECTIVE</b>To study the prevalence of Diabetes mellitus (DM) in children and adolescents and to describe the characteristics on age, gender and district distribution of schoolchildren, in Beijing.</p><p><b>METHODS</b>A cross-sectional screening program the fasting capillary blood glucose (FCBG) was carried out in 19,593 schoolchildren in 7 areas of Beijing from March to October, 2004. According to the WHO diagnostic criteria: DM was set as FCBG < or = 6.1 mmol/L, impaired fasting glucose (IFG) was set as 5.6 mmol/L < or = FCBG < 6.1 mmol/L.</p><p><b>RESULTS</b>The total aggregate age-adjusted prevalence rates of DM and IFG were 5.7 per thousand and 13.5 per thousand, respectively. The prevalence rates of DM and IFG in males were significantly higher than that in females (7.7 per thousand vs. 3.6 per thousand and 26.8 per thousand vs. 11.3 per thousand. DM X2 = 12.27, P = 0.0005; IFG X2 =47.29, P = 0.0000). Among seven districts, East District had the highest prevalence rates of DM and IFG, 8.9 per thousand and 27.4 per thousand (companied high obesity 28.68%) while Ping-Gu District having the lowest ones as 2.0 per thousand and 7.5 per thousand (obese 12.75%) respectively (X2 = 13.75, and X2 = 32.65, P = 0.0002 and P < 0.0001). The DM prevalence rates between districts ranged from 2.0 per thousand to 8.9 per thousand, X2 = 18.94, P = 0.004 and the IFG prevalence of districts ranged from 7.5 per thousand to 27.4 per thousand (X2 = 52.05, P < 0.0001). The prevalence rates of DM among different age groups increased with age, with the highest prevalence of IFG on the 10-14 age group. Among boys, the highest prevalence rates of DM and IFG fell in the 15-18 and 10-14 age groups respectively while the highest prevalence rates on both DM and IFG among girls were in the same age group 10-14.</p><p><b>CONCLUSION</b>The high prevalence rates on DM and IFG were seen in Beijing and showed significant discrimination on age, gender and district distribution. More developed urban district and males had a higher prevalence, companied by higher obesity prevalence. Age seemed to be a high risk factor on DM for boys while the puberty development seemed a high risk factor for girls.</p>
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Adolescente , Criança , Feminino , Humanos , Masculino , China , Epidemiologia , Estudos Transversais , Diabetes Mellitus , Diagnóstico , EpidemiologiaRESUMO
Objective To evaluate the associations of human leukocyte antigen(HLA)-DQ gene with autoimmune polyglandular syndrome(APS),type 1 diabetic mellitus(T1DM) and autoimmune thyroid disease(AITD).Methods Fifteen cases of APS,29 cases of T1DM and 40 cases of AITD were selected as research subjects,while 27 healthy children were selected as controls.The DQA1 and DQB1 alleles were determined by polymerase chain reaction(PCR) and sequence-based typing method.The difference of their frequency in children and adolescents was analyzed.Results Compared with controls,APS and T1DM patients had increased frequency of subjects with DQA1*0301,0501(all P
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<p><b>OBJECTIVE</b>HLA-DMA and DMB are non-classical genes whose product (DM molecules) plays an important role in antigen presentation. Our present study was designed to investigate the relationship between human leukocyte antigen-DMA, -DMB and clinical status heterogeneity of type 1 diabetes.</p><p><b>METHODS</b>A total of 80 children (male 36, female 44) with type 1 diabetes were selected as research subjects. Diagnosis of type 1 diabetes was made according to WHO criteria. The range of age at onset of type 1 diabetes was 2.5 - 14 years. Ninety-one healthy adult blood donors were selected as normal controls. Polymerase chain reaction and dot blot hybridization techniques were used to classify DMA and DMB alleles. Patients with type 1 diabetes were classified into different groups according to different clinical status, including sex, age of onset, ketosis onset situation on diagnosis, remained function of islet beta cell, etc. Then distribution of DM susceptive alleles and heterodimer in different clinical groups were studied.</p><p><b>RESULTS</b>The frequencies of DMA * 0103 and DMB * 0103 alleles in patients were significantly increased (50% vs. 8%, 43% vs. 22%, respectively), these two alleles confer susceptibility to type 1 diabetes in Chinese. The frequencies of DMA * 0103/DMB * 0102, DMA * 0103/DMB * 0103 and DMA * 0103/DMB * 0101 heterodimers were also increased in the patients. The above heterodimers confer predisposition to type 1 diabetes. Both DMB * 0103 allele and DM susceptive heterodimers are related to islet beta cell function on diagnosis. The patients with DMB * 0103 allele or DM susceptive heterodimers were significantly increased in the patients with lower C-peptide level on diagnosis (56% vs. 29%; 58% vs. 34% respectively). DM heterodimes were also related to onset age and ketosis-onset-situations of the patients. The patients carrying DM susceptive heterodimers had higher probability to suffer type 1 diabetes before 10 years of age and had the predisposition to ketosis or ketoacidosis on diagnosis.</p><p><b>CONCLUSION</b>HLA- class II non-classical alleles-DMA and DMB may play an important role in pathogenesis of type 1 diabetes, and clinical status heterogeneity of type 1 diabetes may be related to genetic mechanism.</p>
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Alelos , Diabetes Mellitus Tipo 1 , Genética , Patologia , Frequência do Gene , Antígenos HLA-D , Genética , Reação em Cadeia da PolimeraseRESUMO
Objective To analyze the etiology of diabetes ketoacidosis(DKA) in children with type 1 diabetes.Methods Totally 850 person-time of type 1 diabetes children in recent 20 years in our hospital were selected as studied subjects. Two hundred and twenty-five person-time of them were hospitalized because of DKA.Fifty-six cases (131 person-time) were due to recurrent DKA.These patients were classified into 2 groups according to onset time: group 1(diagnosed from 1982 to 1991) and group 2(diagnosed from 1992 to 2001).Results The analysis of recurrent DKA suggested that 71.8 % of them was due to infection, 20.4 % of them did not obey diabetic diet and 9.2 % of them discontinued insulin injection. The etiology of DKA showed no difference in two groups. The number of recurrent DKA in two groups was significantly different (P