Type 2 spondyloepimetaphyseal dysplasia with joint laxity caused by KIF22 gene mutation: a case report and literature review / 中华骨科杂志

A male patient aged 1 year and 8 months with type 2 spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL2) was reported. The clinical characteristics included short stature, flat middle face, hypotonia, limb joint relaxation, hyperextension of metacarpophalangeal articulation, etc. In addition, the patient had a history of congenital laryngeal stridor. Thus, SEMDJL2 was determined according to the above symptoms and medical history. Sanger sequencing showed that the child carried a c.443C>T missense mutation in the KIF22 gene, which resulted in an amino acid variation namely p.Pro148Leu. This phenotype was preliminarily determined as a pathogenic mutation. Therefore, it is suggested that next-generation sequencing genetic testing could be helpful for genetic diagnosis in children with congenital laryngeal stridor, systemic joint relaxation, and excessive joint extension.

Analysis on clinical and genetic characteristics of children with ATP-sensitive potassium channel congenital hyperinsulinism / 中华胰腺病杂志

Objective:To analyze clinical characteristics and genetic characteristics of children with ATP sensitive potassium passage (K ATP-HI). Methods:Forty-five children with genetically confirmed K ATP-HI and their families admitted to Beijing Children′s Hospital of Capital Medical University between February 2002 and December 2018 were selected as the study subjects. A detailed retrospective analysis of the patient's clinical characteristics, diagnosis and treatment process, disease-causing gene carrying status and later follow-up data was performed. ABCC8/KCNJ11 gene was sequenced by second-generation sequencing technology. Results:Among 45 children with K ATP-HI, 34 cases (75.6%) were neonatal onset, the first symptoms of 21 cases (46.7%) were convulsions. 39 cases had been treated with diazoxide, including 12 cases (30.8%) with good efficacy, 16 cases (41%) with poor efficacy and 11 cases with uncertain efficacy. Octreotide was further applied in 18 patients with uncertain or ineffective efficacy after diazoxide treatment, and 13 cases (72.2%) were effective, 3 cases were ineffective, and 2 cases were uncertain. 10 CHI patients who were ineffective to drug treatment or had clearly focal lesions confirmed by 18F-dopa positron emission by computed tomography ( 18F-DOPA PET) scans had undergone surgical treatment, 8 of which underwent partial pancreatectomy and blood glucose returned to normal after the operation; the other 2 cases underwent subtotal pancreatectomy and both had secondary diabetes after operation. Among 45 children with K ATP-HI, 1 case carried both ABCC8 and KCNJ11 mutations, 10 cases carried ABCC8 compound heterozygous mutations, and the remaining 34 cases carried ABCC8/KCNJ11 single genetic mutation. Among them, 21 cases had paternal inheritance, and 3 cases had maternal inheritance, 6 cases were identified with de novo mutations. Conclusions:Diazoxide treatment was ineffective for most K ATP-HI children, but octreotide had a higher effective rate. Partial pancreatectomy for focal type patients had a higher cure rate, and there was a risk of secondary diabetes after subproximal pancreatectomy, so it was very important to clarify the histological type of children before surgery. ABCC8 gene mutations and KCNJ11 gene mutations were the main pathogenic genes of K ATP-HI. Among patients carrying mutations in single ABCC8 or KCNJ11 gene mutation, K ATP-HI inherited by paternity were the majority. Some K ATP-HI children can relieve the hypoglycemia symptoms by themselves.

Research progress of Hutchinson-Gilford progeria syndrome / 中华实用儿科临床杂志

Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease mainly characterized by accele-rated aging, with an incidence rate of 1 in 8 million to 1 in 4 million.It can affect the skin, fat, cardiovascular, bone and other organ systems.Most HGPS children can only live to 6-20 years old, with an average life expectancy of only 14.6 years.HGPS has distinctive clinical features, such as severe growth retardation, special skin manifestations, and craniofacial manifestations.The prognosis of this disease is poor, and no treatment has been proven effective so far.Upon the diagnosis, the progress of the disease should be observed and monitored via long-term and careful follow up, so as to extend the life span of the children as much as possible.In this article, the disease type, clinical manifestations, pathogenesis and clinical examination of HGPS were reviewed.

Clinical features and genetic mutation analysis in a family of X-linked adrenoleukodystrophy / 中华内分泌代谢杂志

Objective:To analyze the clinical features of a kindred of X-linked adrenoleukodystrophy(X-ALD) with the onset of primary adrenocortical insufficiency, and to detect the mutation of ATP-binding cassette, sub-family D, member l(ABCD1) gene.Methods:A Chinese X-ALD kindred with two affected males from two-generations was studied. The clinical data of the proband′s family members were collected. The sequences of ABCD1 of the proband, his parent and young brother were detected by next-generation sequencing. X-ALD was diagnosed according to clinical manifestations, cranial MRI image, and serum level of very long chain fatty acid(VLCFA).Results:The two cases were all males. The proband was characteristic of primary adrenocortical insufficiency and neurological dysfunction, with extensive cerebral white matter demyelination and high serum VLCFA level. At the age of 2 years and 10 months, the younger brother of the proband presented with primary adrenocortical dysfunction, without neurological symptoms. Gene sequencing results of two patients showed a novel missense substitution(c.1666C>T) in exon 7 of ABCD1 inherited from their mother.Conclusion:The new mutation of ABCDl gene c. 1666C>T may lead to adrenoleukodystrophy. Primary adrenocortical insufficiency and neurological dysfunction are the typical manifestations of X-ALD.

Analysis on six cases of Hutchinson-Gilford progeria syndrome / 中华内分泌代谢杂志

Objective:To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome, and to analyze the pathogenic genes carried by some patients.Methods:The clinical data of 6 patients were summarized. The pathogenic genes of 4 families were analyzed. Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation. The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA) gene and to identify the pathogenic mutation sites by comparing with normal sequencing results.Results:All the children had typical clinical manifestations of the disease which has been previously reported in the literature, such as severe growth retardation, special skin manifestations, and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c. 1824C>T(p.G608G). The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c. 1968+ 2T>C, among which the mutation of IVS8-4 C>A has not been reported.Conclusions:In Chinese children, both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging. It is easy to make a diagnosis based on clinical manifestations. Finding of the pathogenic gene may further confirm the diagnosis.

Clinical and genetic characteristics analysis of Chinese children with glutamate dehydrogenase type of congenital hyperinsulinemia / 中华胰腺病杂志

Objective:To analyze the clinical features and genetic characteristics of Chinese children with glutamate dehydrogenase type of congenital hyperinsulinism (GDH-HI).Methods:Pedigrees with 10 GDH-HI children admitted to Beijing Children′s Hospital from February 2008 to December 2018 were selected as subjects. Clinical features, the detection of pathogenic genes and follow-up data were retrospectively analyzed. Polymerase chain reaction DNA (PCR-DNA) direct sequencing method and second generation sequencing technique were used to analyze the GLUD1 genetic sequences of 10 GDH-HI children and their relatives.Results:Of the 10 GDH-HI children, 9 had normal birth weight and 1 was a giant. Nine patients were accompanied by asymptomatic hyperammonemia, and one had normal blood ammonia. 9 had ever been treated with diazoxide, which was all effective. All 10 children carried GLUD1 gene mutations, 5 patients carried c. 965C>T (p.R322H) GLUD1 gene mutation, and the remaining 5 cases carried c. 1388A>T (p.N463I), c. 1495C>A(p.G499C), c. 1493C>T(p. S498L), c. 1519G>A(p.H507Y) and c. 1388A>G(p.N463S), respectively. 9 cases (90%) had de novo mutations, and 1 case had paternal autosomal dominant inheritance. 8 children were followed up in long term. One child had spontaneous remission in 8 years after being diagnosed, and seven patients required long-term oral diazoxide to maintain normal blood glucose levels, two of whom had epilepsy.Conclusions:The birth weight of children with GDH-HI in China was usually normal. A small number of GDH-HI children had normal serum ammonia levels. Most of the GLUD1 gene mutations in GDH-HI children in China were de novo mutations, among which the GDH p. R322H mutation was a hot spot mutation in Chinese children with GDH-HI. Most of GDH-HI children were diazoxide-responsive. As the disease progresses, some children may have epilepsy, and a few children have a tendency to relieve by themselves.

An analysis of 4 cases with Gitelman syndrome caused by SLC12A3 gene mutation in children / 中华实用儿科临床杂志

Objective:To study the clinical and genetic characteristics of Gitelman syndrome in children.Methods:Four children diagnosed with Gitelman syndrome in the Baoding Children′s Hospital from January 2017 to October 2018 were enrolled, and their clinical data and pathogenic gene carrying status were analyzed.Results:There were 2 males and 2 females in the enrolled patients.Two children complained of short stature and 2 children were diagnosed as hypokalemia by accident.All the 4 children showed constipation, short stature, repeated hypokalemia, hyponatremia, hypochloremia, normal urinary calcium/creatinine ratio, elevated renin and angiotensin Ⅱ levels in supine position, and normal aldosterone.Three children had hypomagnesemia and 1 child had a normal blood magnesium level.All of the 4 children had a compound heterozygous mutation of SLC12A3 gene.The mutations of c. 1670-7G>A and c. 1698C>A were not reported in the literature. Conclusions:Constipation and short stature are common clinical manifestations of Gitelman syndrome in children.Typical cases show hypokalemia, hypomagnesemia, hyponatremia and hypochloremia, etc.The blood magnesium level can be normal in few children.Most children with Gitelman syndrome carry SLC12A3 compound heterozygous mutations.

Clinical and genetic characteristics analysis of Chinese children with glutamate dehydrogenase type of congenital hyperinsulinemia / 中华胰腺病杂志

Objective@#To analyze the clinical features and genetic characteristics of Chinese children with glutamate dehydrogenase type of congenital hyperinsulinism (GDH-HI).@*Methods@#Pedigrees with 10 GDH-HI children admitted to Beijing Children′s Hospital from February 2008 to December 2018 were selected as subjects. Clinical features, the detection of pathogenic genes and follow-up data were retrospectively analyzed. Polymerase chain reaction DNA (PCR-DNA) direct sequencing method and second generation sequencing technique were used to analyze the GLUD1 genetic sequences of 10 GDH-HI children and their relatives.@*Results@#Of the 10 GDH-HI children, 9 had normal birth weight and 1 was a giant. Nine patients were accompanied by asymptomatic hyperammonemia, and one had normal blood ammonia. 9 had ever been treated with diazoxide, which was all effective. All 10 children carried GLUD1 gene mutations, 5 patients carried c. 965C>T (p.R322H) GLUD1 gene mutation, and the remaining 5 cases carried c. 1388A>T (p.N463I), c. 1495C>A(p.G499C), c. 1493C>T(p. S498L), c. 1519G>A(p.H507Y) and c. 1388A>G(p.N463S), respectively. 9 cases (90%) had de novo mutations, and 1 case had paternal autosomal dominant inheritance. 8 children were followed up in long term. One child had spontaneous remission in 8 years after being diagnosed, and seven patients required long-term oral diazoxide to maintain normal blood glucose levels, two of whom had epilepsy.@*Conclusions@#The birth weight of children with GDH-HI in China was usually normal. A small number of GDH-HI children had normal serum ammonia levels. Most of the GLUD1 gene mutations in GDH-HI children in China were de novo mutations, among which the GDH p. R322H mutation was a hot spot mutation in Chinese children with GDH-HI. Most of GDH-HI children were diazoxide-responsive. As the disease progresses, some children may have epilepsy, and a few children have a tendency to relieve by themselves.

Analysis on six cases of Hutchinson-Gilford progeria syndrome / 中华内分泌代谢杂志

Objective@#To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome, and to analyze the pathogenic genes carried by some patients.@*Methods@#The clinical data of 6 patients were summarized. The pathogenic genes of 4 families were analyzed. Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation. The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA) gene and to identify the pathogenic mutation sites by comparing with normal sequencing results.@*Results@#All the children had typical clinical manifestations of the disease which has been previously reported in the literature, such as severe growth retardation, special skin manifestations, and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c. 1824C>T(p.G608G). The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c. 1968+ 2T>C, among which the mutation of IVS8-4 C>A has not been reported.@*Conclusions@#In Chinese children, both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging. It is easy to make a diagnosis based on clinical manifestations. Finding of the pathogenic gene may further confirm the diagnosis.

Therapeutic efficacy analysis of diazoxide in treating 145 cases of congenital hyperinsulinism / 中华胰腺病杂志

Objeetive To analyze the efficacy and safety of diazoxide treatment in patients with congenital hyperinsulinism (CHI).Methods The clinical data of 145 patients diagnosed with CHI hospitalized in Beijing Children's Hospital affiliated to Capital Medical University from February 2002 to January 2016 who received diazoxide treatment were retrospectively analyzed.We conducted a detailed analysis on the efficacy,side effects and prognosis of diazoxide treatment for CHI.Results In 145 patients,there were 89 patients (61.4％) who were responsive to diazoxide and 23 patients (15.9％) unresponsive to diazoxide,and the treatment effect of diazoxide for the other 33 cases (22.8％) was still unclear.In the diazoxide effective group,there were 22 cases (24.7％) of neonatal onset,32 cases (36.0％)of onset from 1-6 months after birth and 35 cases (39.3％) of onset after 6 months of birth,and the birth weight was normal in 67 cases,macrosomia in 16 cases,low in 5 cases and unknown in 1 case.In the diazoxide ineffective group,there were 14 cases (60.8％) of neonatal onset,7 cases (30.4％) of onset from 1-6 months after birth and 2 cases (8.6％)of onset after 6 months of birth,and the birth weight was normal in 9 cases and macrosomia in 14 cases.In the unclear diazoxide effect group,there were 20 cases (60.6％) of neonatal onset,9 cases (27.34％) of onset from 1-6 months after birth and 4 cases (12.1％) of onset after 6 months of birth,and the birth weight was normal in 15 cases and macrosomia in 18 cases.After the application of diazoxide,65 cases (44.8％) had hirsutism,and 43 patients (29.7％) had gastrointestinal side effects.In the diazoxide effective group,the symptom of hypoglycemia was spontaneously alleviated at the age of from 3 months to 7 years old in 20 patients (22.5％),and 33 patients continued to be treated by diazoxide.In the diazoxide ineffective group,the symptom of hypoglycemia was spontaneously alleviated around the age of 1 years old in 4 patients (17.3％),5 patients were treated by octreotide in long term to maintain normal blood sugar level,4 patients received pancreectomy including 3 with normal blood sugar and 1 with occasional hypoglycemia after surgery.In the unclear diazoxide effect group,the symptom of hypoglycemia was spontaneously alleviated at the age of from 10 months to 3 years old in 4 patients (12.1％),2 patients were treated by octreotide in long term to maintain normal blood sugar level,8 patients received pancreatectomy including 5 with controlled blood sugar after surgery.Conclusions Diazoxide is effective in treating CHI children.The efficiency may be higher for the CHI with normal birth weight or whose onset age is after the neonatal period.

Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome

Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA mutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively. While ESCs and endothelial cells (ECs) did not present any features of premature senescence, HGPS- and WS-mesenchymal stem cells (MSCs) showed aging-associated phenotypes with different kinetics. WS-MSCs had early-onset mild premature aging phenotypes while HGPS-MSCs exhibited late-onset acute premature aging characterisitcs. Taken together, our study compares and contrasts the distinct pathologies underpinning the two premature aging disorders, and provides reliable stem-cell based models to identify new therapeutic strategies for pathological and physiological aging.

Clinical characteristics and gene mutations analysis of 56 patients with congenital hyperinsulinism / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and gene mutations of 56 patients with congenital hyperinsulinism(CHI)and to provide a theoretical basis for clinical diagnosis and treatment of CHI.Methods Fifty-six children who were diagnosed as CHI between February 2002 and January 2016 in Beijing Children's Hospital Affiliated to Capital Medical University were selected as research subjects.A retrospective study was done about the clinical data and the treatment procedures of the 56 patients,such as perinatal conditions,clinical manifestations,laboratory data,treatments,prognosis and so on.Polymerase chain reaction(PCR)-DNA technology or next-generation sequencing technology was used to analyze the CHI relevant genes of the 56 patients.Results Thirty of the 56 patients carried CHI gene mutation.(1)Twenty-three of 56 patients(41.0％)carried ABCC8/KCNJ11 gene mutations:4 of 23 patients carried complex heterozygous mutation,1 of 23 patients carried both ABCC8 and KCNJ11 gene mutation,1 of 23 patients carried maternally inherited ABCC8 gene mutation,12 of 23 patients carried paternally inherited ABCC8 gene mutation,1 of 23 patients carried paternally inherited KCNJ11 gene mutation,3 of 23 patients carried de novo ABCC8 gene mutation,1 of 23 patients had unknown genetic way,19 of 23 patients were treated with Diazoxide,2 of 19 patients were responsive to Diazoxide,7 of 19 patients were unresponsive to Diazoxide and 10 of 19 patients were uncertain to Diazoxide.(2)Five of 56 patients(8.9％)carried GLUD1 gene mutation,4 of 5 patients were treated with Diazoxide and they were all responsive to Diazoxide.(3)One of 56 patients(1.7％)carried de novo GCK gene mutation,responsive to Diazoxide treatment.(4)One of 56 patients(1.7％)carried maternally inherited SLC16A1 gene mutation,responsive to Diazo-xide treatment.Conclusions The ABCC8 gene and GLUD1 gene mutation are the main causative genes of CHI.The GCK gene and SLC16A1 gene mutation are in the minority.Most ABCC8 gene and KCNJ11 gene mutation are unresponsive to Diazoxide treatment.

Clinical analysis of 194 patients with congenital hyperinsulinism / 中华实用儿科临床杂志

Objective To summarize the clinical data of 194 patients with congenital hyperinsulinism(CHI),in order to provide the theoretical basis for the diagnosis,treatment and prognosis of CHI.Methods One hundred and ninety-four patients with CHI hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University from February 2002 to January 2016 were recruited.Clinical data of 194 patients were collected and clinical characteristics and treatment were retrospectively analyzed.Results One hundred and forty-four cases in 194 patients were treated with Diazoxide,among whom,88 cases were responsive to Diazoxide,23 cases were unresponsive to Diazoxide,and 33 cases were uncertain to Diazoxide.Twenty-six cases in 194 cases were treated with Octreotide,among whom,16 cases were responsive to Octreotide,5 cases were unresponsive to Octreotide,and 5 cases were uncertain to Octreotide.Eleven cases in 194 cases had the 18 Fluoride-L-dihydroxyphenylalanine positron emission computerized tomography scan (18-F-L-DOPA-PET scan),among whom,7 cases were identified as focal lesion and 4 cases were identified as diffuse lesion.Twelve cases in 194 cases were treated with pancreatectomy,among whom,4 cases achieved normal blood glucose levels,4 cases still suffered from persistent hypoglycemia,3 cases had type 1 diabetes mellitus,and 1 case dropped out after the surgery.Forty-five cases in 194 cases had spontaneous remission and the remission time varied from 1 month to 8 years.Conclusions (1) Diazoxide is the first line drug of CHI.The older age onset is,the higher possibility of responsive to Diazoxide shows.(2)Octreotide is used as the second line drug.(3)18-F-L-DOPA-PET scan is the first choice to identify the location of CHI and it is useful in distinguishing between focal and diffuse forms.(4) The outcome of CHI patients after pancreatectomy is very different.A proper surgical method should be selected before the surgery.The blood glucose should be detected after surgery for a long time.(5) Some patients have the tendency of spontaneous remission.

Genetic pathogenesis and current trends in diagnosis and therapy of ATP-sensitive potassium channel congenital hyperinsulinism / 中华实用儿科临床杂志

ATP-sensitive potassium channel congenital hyperinsulinism (KATP-HI) is the most common and most severe type of congenital hyperinsulinism,accounting for 40％-45％.It is due to the inactivating mutations of the ABCC8 and KCNJ11 gene which encode the ATP-sensitive potassium channel.Diazoxide is the main and preferred therapy for KATP-HI.For KATP-HI children who are unresponsive to medical therapy usually need different degrees of pancreatectomy to maintain normal blood sugar level.

Scanning and analysis of the KATP channel mutations in 12 cases of infancy onset type 1 diabetes mellitus / 中华实用儿科临床杂志

Objective To screen the mutation of KATP channel mutations in Chinese pedigrees with infantile onset type 1 diabetes mellitus (T1DM) and neonatal diabetes mellitus.Methods A cohort of 12 children of infant onset T1DM and neonatal diabetes mellitus admitted into Beijing Children's Hospital between March 2004 and June 2013 were selected.PCR amplification and direct sequencing were used to analyze the 39 exons of ABCC8 gene and one exon of KCNJ11.And the mutational sites of the parents of the probands was sequenced in order to identify the inheritance.Results Analysis revealed ABCC8 mutation in 25％ (3/12 cases) of the patients,a case of transient neonatal diabetes (TNDM),a case of permanent neonatal diabetes mellitus (PNDM) and a case of infant onset T1DM.All positive patients showed a known heterozygosis mutation in the ABCC8 gene(R1182Q,c.3545G ＞ A,D209E,c.627C ＞ G,E208K c.622G ＞ A).The residue R1182Q,which was located at a position involved in joining transmembrane domain 2 to nucleotide binding domain 2,the mutations E208K and D209E were located in the intracellular region that links the transmembrane domain with the gatekeeper module.All the three mutations were located throughout the cytoplasm part of SUR1 protein.The TNDM successfully transferred from insulin to oral sulfonylureas therapy.Conclusions There is a complex genetic pathogenesis in neonatal and infant-onset diabetes.The KATP channel activating mutations is one of the main causes of neonatal diabetes mellitus and may cause T1DM in infants in China.Oral Glibenclamide therapy seems highly effective for some patients with the KATP channel activating mutations.

Clinical analysis on 18 children with neonatal bartter syndrome / 中国医师杂志

Objective To analyze the clinical characteristics of Neonatal Bartter syndrome in order to enhance understanding of the disease.Methods Eighteen children with Neonatal Bartter syndrome who were admitted into our hospital from November 2006 to July 2013 were selected as research subjects.A ret-rospective study was done on the clinical data and the outcome of treatment.Results ⑴Clinical character-istics This group included 13 males and 5 females.The onset age ranged from birth to 1 years 3 months (4.01 ±4.49years).Six cases got the disease after birth.Amniotic fluid which lead to premature birth and low birth weight may happened in cases.The most common clinical symptom was malnutrition (89%).⑵Laboratory tests and Renal ultrasound All of the children showed hypokalemia and metabolic alkalosis in some degree,renin and angiotensin increased.In some cases urinary calcium /creatinine ratio were in-creased and urinary specific gravity,showed a low proportion of urine.Some cases'renal ultrasound exami-nation revealed nephrocalcinosis.⑶ Therapy:All of the patients in this group were given intravenous and /or oral potassium chloride treatment.For drug treatment,10 cases were given single application of indom-ethacin [1 ~3mg/(kg·d),points 3 times per day oral]treatment.Conclusions The incidence of Neo-natal Bartter syndrome was early in infant onset as early as after birth,even the fetal period.Some patients may appear premature birth and /or low birth weigh because of amniotic fluid.The main clinical manifesta-tions include malnutrition,no weight increasing,retardation,serious dehydration and even life-threatening. The characteristic appearance such as the forehead,small jaw,eyes are the important characteristics of neo-natal Bartter syndrome.Patients often appears Hypokalemia,hyponatremia and Hypochloremia.Urinary po-tassium of this type increased.Most children's urinary sodium and chloride increased significantly.

Fourteen cases of children with craniopharyngiomas / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and the endocrine changes in children with craniopharyngioma,and to improve the pediatrician understanding of the disease.Methods The study subjects consisted of 14 children with craniopharyngioma admitted to the Department of Endocrinology,Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2004 to Dec.2012.All the patients were followed up to analyze the clinical symptoms improvement,endocrine test results and medication,et al.Results The main clinical manifestations were headache (7/14 cases,50.0％),growth retardation(4/14 cases,28.6％),vomiting (4/14 cases,28.6％),polydipsia/ polyuria (3/14 cases,21.4％) and vision diminution (3/14 cases,21.4％).Three patients didn' t undergo the surgery,and 3 cases with diabetes insipidus and 2 cases with growth hormone deficiency,and 1 case with central hypothyroidism by laboratory test.The rest 11 children received surgery and all patients had changes in endocrine after it.Five cases got polydipsia and polyuria,other 5 cases had electrolyte disturbances,and 2 cases had epilepsy.Nine patients were followed up,and the follow-up duration ranged from 5 months to 10 years [(3.29 ± 3.52) years] after surgery.Seven patients got better and 2 patients got worse.Conclusions For clinical symptoms of increased intracranial pressure,changes in endocrine,the vision and visual field,the possibility of craniopharyngioma should be taken into account.Surgery is the main treatment,but it can lead to the damage of hypothalamus and pituitary gland.Changes in endocrine,electrolyte disturbances and epilepsy are the common complications.According to the level of endocrine,longterm hormone replacement therapy for some postoperative patients should be continued.

Clinical analysis of 9 children with Pseudo-Bartter syndrome / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics of children's Pseudo-Bartter syndrome(PBS) in order to enhance physician's understanding of the disease.Methods Nine children with PBS who were admitted into Beijing Children's Hospital from Nov.2008 to Sep.2013 were selected as research subjects.A retrospective study was carried out with the clinical data and the outcome of treatment.Results 1.Clinical characteristics:there were 9 cases in this group including 5 male and 4 female.The patients' age ranged from 4 months to 8 years 8 months.The most common cause of children's PBS was gastrointestinal symptoms(such as diarrhea and vomiting) induced by respiratory tract infection (7/9 cases).Six patients had no striking clinical manifestations,and hypokalemia was found in the treatment of primary disease.2.Laboratory tests:All of the children in this group had hypokalemia and metabolic alkalosis in varying degrees.The activation of renin,angiotensin and aldosterone system increased.3.Therapy:all children were treated by giving potassium supplemental treatment or indomethacin therapy [1 mg/(kg · d),3 times orally].After treatment,all cases achieved clinical improvement and normal blood electrolytes.All patients' blood electrolytes remained normal for 5 to 7 days after stopping treatment.Conclusions 1.In China,the most common cause of children's PBS is gastrointestinal symptoms(such as diarrhea and vomiting) induced by respiratory tract infection.2.Except for clinical manifestations related to causes,patients have no significant clinical manifestations.Hypokalemia can be found in the treatment of primary disease.3.The biochemical results show low blood potassium chloride with metabolic alkalosis.In PBS renin,angiotensin and aldosterone concentration in blood are all elevated.4.Treatment of children's PBS mainly includes etiological treatment and electrolyte supplement therapy.The treatment effectiveness is good after etiological treatment and potassium supplement treatment.In the condition of controlling etiology and potassium supplementation,electrolytes mas return to normal in 2-4 days.

An ABCC8 gene mutation leading to the onset of KATP-congenital hyperinsulinism in a Chinese boy and his pedigree analysis / 中华内分泌代谢杂志

ABCC8,KCNJ11,and GLUD1 gene mutations were investigated in a male patient with congenital hyperinsulinism and his parents were also investigated.A 1484 G＞A mutation was found in the 10th exon of ABCC8 gene in the patient,which leads to amino acid substitution at the 495 residue of the sulphonylurea receptor SUR1 protein.The patient's father also carried the same heterozygous inactive mutation,while the genotype of the mother was normal,indicating that the gene mutation of the patient was paternally inherited.According to that mutation,it is deduced that the patient may suffer from the focal type of congenital hyperinsulinism.

KCNJ11 gene mutation in 3 cases with neonatal diabetes mellitus / 中华内分泌代谢杂志

KCNJ11 gene mutation was searched in 3 families with neonatal diabetes. A KCNJ11 175 G>A (V59M) mutation was found in one child, while no KCNJ11 gene mutation was found in his parents. No mutation was found in the other two families. The result indicated that KCNJ11 gene mutation might lead to the onset of neonatal diabetes mellitus in Chinese.