Congenital glycosylation disorders: a study of two patients

BackgroundCongenital glycosylation disorders (CGDs) are a group of disorders caused by a defect in glycoprotein synthesis. Clinical manifestations may affect to different organs.AimsTo describe two new patients cases with a CGD in order to make paediatricians aware of this disorder.Clinical casesTwo new cases of different age and gender are presented, showing clinical manifestations, and radiological and laboratory findings compatible with CGD. One of the cases was followed up for several years.ConclusionsGlycosylation disorders are a group of conditions to bear in mind when considering the diagnosis of a patient with neurological symptoms of unexplained origin, particularly in those cases that include a delay in psychomotor activity, low muscle tone, epilepsy, and hepatic or coagulation disorders, as well as in patients with cerebellar or olivopontocerebellar atrophy.     

Management of febrile neutropenia in pediatric oncology patients: a Canadian survey

BACKGROUND: Traditionally, febrile neutropenia in pediatric oncology patients has been managed aggressively with hospital admission and intravenous antibiotics. Recent studies suggest that less intensive interventions are effective for selected children. Study of Canadian practice patterns may help better understand the current context of care for these patients. PROCEDURE: We carried out a cross-sectional mailed survey of the 17 tertiary pediatric centers in Canada. A 36-item questionnaire gathered information on oncology department characteristics, the existence of protocols for management of febrile neutropenia, use of outpatient therapy or early discharge, criteria used to identify patients at low risk, and opinions of oncologists. RESULTS: A total of 16 (94%) completed questionnaires were returned, reflecting a treatment population of approximately 2,100 children with febrile neutropenia/year. Three out of seventeen centers carry out exclusively traditional management. The remaining 14 offer modified treatment for low risk children. The majority (n = 10) carry out an early discharge approach. Two thirds of the episodes of febrile neutropenia are treated this way with good results. The rest (n = 4) implement complete outpatient management. Approximately 120 patients benefit from this annually, with a reportedly high success rate. Most specialists agreed on the benefits of decreased hospitalization for children with cancer. However, about half considered the level of evidence is not sufficient to fully implement complete outpatient management. CONCLUSIONS: Variations in the treatment of pediatric febrile neutropenia have been extensively implemented across Canada. However more evidence, ideally in the form of multicenter clinical trials, appears to be needed to further safely modify practice.     

Diagnostic approach to primary immunodeficiency disorders

Primary immunodeficiency disorders (PIDs) are a heterogeneous group of inherited disorders that affect different components of the immune system. There are more than 150 different disorders which have been described till date. Despite major advances in the molecular characterization of PIDs over the last 20 years, many patients remain undiagnosed or are diagnosed too late with severe consequences. Recognizing different clinical manifestations of PID is the first most important step. It should be followed by use of appropriate diagnostic tools from a vast number of investigations available. This review will focus on important presenting features of PID and laboratory approach for diagnosis of suspected cases of PID.     

Lymphocyte subpopulations in primary immunodeficiency disorders.

Venous blood mononuclear cells from 42 children with primary immunodeficiency disorders and from controls matched for age were studied for lymphocyte subpopulations by E rosetting, surface immunoglobulin, and a panel of anti T cell monoclonal antibodies (OKT series). In 3 cases of severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency, very few circulating T or B cells were found. The other 7 cases of SCID all had normal or, in 3 cases, very high numbers of circulating B cells, but in 6 of these very few cells showed T cell markers. One child had very high numbers of B cells and T cells with an immature pattern of reactivity similar to that found on common thymocytes. In T cell deficient children no consistent pattern was found, but in those with cartilage hair hypoplasia with immunodeficiency there was a low helper (OKT4) to suppressor (OKT8) ratio and high numbers of circulating OKT10 positive cells. In cases of X-linked agammaglobulinaemia circulating B cells were not found but the pattern of T cell markers was normal. In cases of common variable hypogammaglobulinaemia there was a wide scatter of helper (OKT4) to suppressor (OKT8) cell ratios. Five children were studied before and after treatment with the synthetic thymic hormone preparation TP5. There were appreciable alterations in the pattern of staining with anti T cell monoclonal antibodies in 4 of these cases, but in 1 case only was this accompanied by improvements in clinical and immune function.     

Congenital disorders of glycosylation: a review

Congenital disorders of glycosylation (CDGs) are a rapidly growing group of inherited disorders caused by defects in the synthesis and processing of the asparagine(ASN)-linked oligosaccharides of glycoproteins. The first CDG patients were described in 1980. Fifteen years later, a phosphomannomutase deficiency was found as the basis of the most frequent type, CDG-Ia. In recent years several novel types have been identified. The N-glycosylation pathway is highly conserved from yeast to human, and the rapid progress in this field can largely be attributed to the systematic application of the knowledge of yeast mutants. Up to now, eight diseases have been characterized, resulting from enzyme or transport defects in the cytosol, endoplasmic reticulum, or Golgi compartment. CDGs affect all organs and particularly the CNS, except for CDG-Ib, which is mainly a hepatic-intestinal disease.     

原发性免疫缺陷病临床发病情况回顾

目的了解原发性免疫缺陷病的临床发病情况,加强临床医师对该类疾病的认识,促进今后防治工作的开展.方法回顾性分析1974年1月至2003年12月我院93例原发性免疫缺陷病患儿的临床资料.结果93例原发性免疫缺陷病患儿中,以抗体缺陷为主者占39.8%（37/93）;以联合免疫缺陷者占22.6%（21/93）;以T淋巴细胞缺陷为主者占14.0%（13/93）;其他明确的免疫缺陷综合征者占12.9%（12/93）;吞噬功能缺陷者占9.7%（9/93）;补体缺陷者占1.1%（1/93）.从年度诊断的原发性免疫缺陷病病例数来看有逐年增多的趋势,1996年以后诊断例数呈现大幅度上升,共诊断50例.死亡病例共计16例,以联合免疫缺陷病为主.男：女=3：1.结论我国各类原发性免疫缺陷病均有发病,并且随着诊断技术水平的不断提高,临床诊断的病例日益增多,已成为临床,特别是儿内科的一组重要的疾病,应引起全国临床医师的注意.     

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目的 分析儿童原发性免疫缺陷病(PID)的临床发病及诊断情况,增强儿科医师对该类疾病的认识.方法 回顾性分析重庆医科大学附属儿童医院1993年5月至2007年12月诊断的135例PID患儿的临床资料,包括发病时症状体征、性别、发病年龄、家族史、免疫学结果 及诊断情况.结果 135例患儿中以抗体缺陷最多,占34.8%.吞噬细胞缺陷占18.5%,其他明确的免疫缺陷综合征占14.8%,联合免疫缺陷占11.9%,免疫失调性疾病占5.9%,补体缺陷占0.7%,其他PID占13.3%.男女比例为110:25,临床诊断与基因诊断比例为98:37.1993-1996年诊断9例,1997-2000年诊断23例,2001-2003年诊断31例,2004-2007年诊断72例,诊断病例数逐年增加.其中2001-2003年基因诊断7例,2004-2007年基因诊断30例.结论 PID为一组主要见于婴幼儿的遗传病,是引起儿童反复、严重、致残、致死性感染的重要原因.近年来诊断的PID病例数逐年增加,基因分析是确诊该类疾病的重要手段.     

First nationwide survey of prevalence of weight disorders in Iranian children at school entry

Background  

For the first time, not only in Iran but also in the Eastern Mediterranean region, we report the prevalence of underweight and overweight among all children at school entry.     

儿童原发免疫缺陷病72例临床分析

目的了解儿童原发免疫缺陷病的临床特点。方法回顾分析2000-10—2006-10在北京儿童医院病房收治的原发免疫缺陷病患儿的临床资料。结果72例原发免疫缺陷患儿中以抗体缺陷为主的免疫缺陷病41例(57·0%),联合免疫缺陷病16例(22·2%),吞噬细胞数量和(或)功能缺陷8例(11·1%),以T细胞缺陷为主的免疫缺陷病4例(5·6%),定义明确的免疫缺陷综合征3例(4·2%)。其共同特点为反复的、严重的、持久的感染,但病因不同,又有其各自的特点。如寻常变异型免疫缺陷病病史长者易合并肝脾大及关节炎。严重联合免疫缺陷病发病年龄小,病死率高,除呼吸道感染外,迁延性腹泻较多见;而慢性肉芽肿病以反复的皮肤、淋巴结脓肿及易发生卡介苗播散性疾病为特点。结论原发免疫缺陷病以抗体缺陷为主。部分类型有其独有特点,根据症状、体征可进行相应的检查以明确诊断。约1/4患儿有阳性家族史,对此类患儿应慎重预防接种,以免为患儿造成不必要的痛苦。目前原发免疫缺陷病患儿管理仍极不完善,大量患儿失访或放弃治疗,形势严峻,亟待改善。     

Congenital disorders of glycosylation: a booming chapter of pediatrics

PURPOSE OF REVIEW: The detection and identification of new congenital disorders of glycosylation continues at a rapid pace. Sine June 2003, four new congenital disorders of glycosylation have been reported, making a total of 20 diseases (on average nearly 1 disease per year since the first report in 1980; 12 of these congenital disorders of glycosylation were identified in the past 6 years). RECENT FINDINGS: Three of these newly discovered CDG are caused by defects in early steps of dolichol-linked oligosaccharide biosynthesis. Affected patients have a neurologic or a multisystem disease. The fourth new CDG is a completely new CDG type caused by a defect in an endoplasmic reticulum-Golgi shuttle protein carrying multiple glycosyltransferases and nucleotide-sugar transporters. SUMMARY: Disorders of nearly all organs and systems have been reported and continue to be reported in congenital disorders of glycosylation. Therefore, it is strongly recommended that congenital disorders of glycosylation be considered in any child with an unexplained clinical syndrome.     

Congenital diaphragmatic hernia: a survey of practice in Scandinavia

There is no consensus on the treatment of congenital diaphragmatic hernia (CDH), and practice seems to vary between centres. The main purpose of the present study was to survey current practice in Scandinavia. Thirteen paediatric surgical centres serving a population of about 22 million were invited, and all participated. One questionnaire was completed at each centre. The questionnaire evaluated management following prenatal diagnosis, intensive care strategies, operative treatment, and long-term follow-up. Survival data (1995-1998) were available from 12 of 13 centres. Following prenatal diagnosis of CDH, vaginal delivery and maternal steroids were used at eight and six centres, respectively. All centres used high-frequency oscillation ventilation (HFOV), nitric oxide (NO), and surfactant comparatively often. Five centres had extracorporeal membrane oxygenation (ECMO) facilities, and four centres transferred ECMO candidates. The majority of centres (7/9) always tried HFOV before ECMO was instituted. Surgery was performed when the neonate was clinically stable (11/13) and when no signs of pulmonary hypertension were detected by echo-Doppler (6/13). The repair was performed by laparotomy at all centres and most commonly with nonabsorbable sutures (8/13). Thoracic drain was used routinely at seven centres. Long-term follow-up at a paediatric surgical centre was uncommon (3/13). Only three centres treated more than five CDH patients per year. Comparing survival in centres treating more than five with those treating five or fewer CDH patients per year, there was a tendency towards better survival in the higher-volume centres (72.4%) than in the centres with lower volume (58.7%), p =0.065.     

Severe combined immunodeficiency (SCID) associated neutropenia: a lesson from monozygotic twins

A case of severe combined immunodeficiency (SCID) in monozygotic twin sisters was detected at 3 months of age with neutropenia in one twin and a normal differential count in the other. The neutropenic twin, suffering from severe skin ulcers, was successfully treated with granulocyte colony stimulating factor (G-CSF). Discordant occurrence of neutropenia in identical twins shows that there may be a non-genetic cause for the neutropenia in SCID. Suppression of myelopoiesis was probably induced by activated maternal T cells. The neutropenia in this case may thus be classified as SCID associated neutropenia, as opposed to reticular dysgenesis, in which the neutropenia is G-CSF refractory and is most probably caused by a genetic stem cell defect. A response to G-CSF in a neutropenic child with SCID can be clinically beneficial and might help to distinguish between G-CSF unresponsive reticular dysgenesis and G-CSF responsive SCID associated neutropenia.     

先天性糖蛋白糖基化缺陷导致的疾病

先天性糖蛋白糖基化缺陷(congenital disordersof glycosylation,CDG)是一组由常染色体隐性遗传引起的糖蛋白合成缺陷而导致的疾病,可引起一系列临床表现[1]。糖蛋白的蛋白糖基化修饰是一个极其复杂的过程,参与其中的酶种类繁多。糖蛋白糖基化缺陷可累及多个脏器,如神经、造血、消化和生殖系统等,从而引起多种多样的临床表现。该病最早由比利时儿科医师Jaeken等[2]于1980年首次报道。迄今根据缺陷的酶、缺陷部位已报道有19型,见表1。1CDG的分型糖蛋白由糖链和多肽链组成,其糖链又有O!糖苷键连接的糖链和N!糖苷键连接的糖链2种。CDG患者…