噬血细胞综合征45例临床分析

目的探讨噬血细胞综合征(HPS)患者的临床特征。方法回顾性分析45例HPS患者的病因、临床及实验室检查特征、治疗反应及转归。结果诱因:单纯病毒感染9例,结核感染2例,自身免疫性疾病相关4例,继发于恶性肿瘤22例,病因不明8例。临床主要表现为高热(93.3%)、肝肿大(77.8%)、脾肿大(80%)、淋巴结肿大(55.6%)、皮疹(24.4%)、消化道出血(22.2%)、肾脏(35.6%)和神经系统受累(15.6%),并发弥漫性血管内凝血(DIC)5例(11.1%)。实验室检查表现为不同程度的血细胞减少(100%)、肝功异常(77.8%)、高三酰甘油血症(71.1%)、低纤维蛋白原血症(62.8%)、铁蛋白>500μg/L(87.5%)和NK细胞活性降低(92.9%)。骨髓检查均可见成熟的单核巨噬细胞吞噬血细胞现象。积极治疗原发病以及经糖皮质激素、免疫抑制剂、人免疫球蛋白等治疗后,好转14例,在院死亡19例,病情加重放弃治疗出院12例。结论HPS病因复杂,临床表现多样,病情凶险,病死率高,积极针对原发病治疗及糖皮质激素、免疫抑制剂、人免疫球蛋白治疗可改善预后。     

杭州地区2010年手足口病临床流行病学特征分析

目的对杭州市2010年4月至10月儿童手足口病（HFMD）的临床流行病学特征进行分析。方法对1848例收治入院手足口病病例进行临床流行病学分析。结果手足口病发病年龄以3岁以下为主,男性多于女性,群居高于散居,乡村高于城镇;发病高峰为5～7月份;临床症状大多轻微,预后良好。结论手足口病有明显的易感人群和易感季节,流行季节加大对易感地区及人群进行健康干预,早期发现,积极治疗,大部分预后良好。     

Castleman病8例临床分析

目的探讨Castleman病的临床特征、实验室检查特点及治疗方案。方法回顾性分析8例Castleman病的临床表现、实验室检查、治疗及疗效评价。结果 8例患者中4例首发症状有乏力,3例有低蛋白血症,3例有蛋白尿或者肾损害,2例有感染,1例有肌损害。3例确诊为透明血管型,3例为浆细胞型,2例为混合细胞型。病理学提示淋巴结结构保持完整,滤泡增生明显,血管增生。结论 Castleman病临床表现无特异性,其诊断和分型主要依靠组织病理学,手术、化疗、放疗及生物治疗等多种方法可应用于该病的治疗。     

新生儿糖尿病（NDM）合并酮症酸中毒（DKA）5例临床特点分析

目的总结分析5例新生儿糖尿病（NDM）合并酮症酸中毒（DKA）的临床特点和转归。方法对2008年9月至2013年3月青岛市妇女儿童医院诊治的5例NDM合并DKA的临床表现、实验室检查及临床转归进行回顾性分析总结，结合国内文献总结其特点。结果5例患儿的平均出生体重为2.4kg，诊断年龄中位数为43d，均在生后3个月内起病，初诊血糖均值为47.02mmol／L，5例主要表现为体重不增甚至消瘦，营养不良，精神不振，反应低下，发现血糖高而就诊，5例均发生酮症酸中毒（DKA）。l例同时伴有先天性心脏病（房间隔缺损），2例伴有高甘油三酯血症，所有患儿急性期均按照《中华医学会儿科学分会内分泌遗传代谢学组儿童糖尿病酮症酸中毒（DKA）诊疗指南（2009年版）》接受快速输液，胰岛素治疗和补钾处理，胰岛素初始治疗剂量为0.05-0.1U／（kg·h），治疗24h内血糖均明显下降，5例合并DKA患儿的酸中毒症状均在治疗48h后缓解，血糖控制良好，急性期无1例死亡。5例中2例符合暂时性NDM（TNDM），随访至今（最短4个月，最长4年），1例在5个月大时，可逐渐停用胰岛素治疗，定期血糖监测正常，目前仍处于随访中；1例4个月大时可逐渐停用胰岛素治疗，随访至4岁，定期血糖监测正常，未再出现临床症状；1例曾口服格列本脲，但血糖未能控制，在4个月大时失访，2例于2个月大时自行停用胰岛素治疗，近4个月时酮症酸中毒死亡。结论对于新生儿期及婴儿期酮症酸中毒的患儿及时行微量血糖和血气分析、生化、电解质、尿常规、糖代谢等检查；NDM合并DKA早期诊断和治疗可使患儿存活；临床上确诊该病应注意与应激性高血糖、医源性或其他原因的高血糖症相鉴别；基因检测不但有助于临床分型，更重要的是可根据不同致病基因进行靶向治疗，能更好控制血糖，减少     

肺结核并糖尿病的临床比较研究

目的了解肺结核合并糖尿病的相互影响、临床表现、治疗和预后.方法对同期的60例肺结核并糖尿病患者(A组)与66例单肺结核患者(B组),以同一方案治疗,比较两组的临床症状、胸部X线表现、实验室检查及治疗效果.结果 A组临床症状较严重,病变以渗出、干酪病灶为主,范围广,痰菌阳性率高,进展快.A组痊愈率、好转率、痰菌阴转率均低于B组.结论及时控制血糖水平、加强抗痨治疗有助于改善糖尿病合并肺结核患者的预后.     

主动脉夹层52例临床分析

目的 探讨主动脉夹层﹙aoriyic dissetionAD﹚的临床表现、诊断、治疗和预后.方法 对52例AD患者的临床资料进行总结,分析其临床特点、、辅助检查、影像学诊断、治疗方法及效果.结果 52例AD患者临床表现多样,胸背部疼痛或腹痛为首发症状.高血压是AD患者AD的主要原因.螺旋CT血管成像诊断符合率达100%.AD的治疗包括积极控制血压、外科手术、支架植入术.结论 对疑诊AD患者应尽快确诊并合理选泽治疗方法,是提高AD生存率和改善预后的关键.     

酷似Reye综合征先天性高氨血症并高乳酸血症一例

报道1例先天性高氨血症并高乳酸血症新生儿,临床表现酷似Reye综合征,抢救成功,随访至1岁,近期预后好。临床上对不明原因的严重酸中毒、高氨血症、高乳酸血症患儿,应及时送尿有机酸及血浆氨基酸分析,排除有机酸血症及氨基酸代谢异常病。     

妊娠急性脂肪肝的临床诊治分析

目的探讨妊娠急性脂肪肝的临床诊断和治疗方法。方法对我院收治的30例妊娠急性脂肪肝患者的临床资料进行回顾性分析。结果30例妊娠急性脂肪肝患者均发生于妊娠晚期,有明显的临床症状和实验室检查特征。剖宫产终止妊娠加内科综合支持治疗能降低产后出血发生率、孕产妇死亡率、围产儿死亡率、新生儿窒息发生率。结论结合临床症状、实验室检查特征、肝脏B超、CT检查等,力争在发病1周内明确诊断,并立即行剖宫产术终止妊娠、积极内科综合支持治疗是改善母儿预后的关键。     

FOXP3基因变异致X连锁多内分泌腺病肠病伴免疫失调综合征3例患儿的临床及遗传学研究

目的分析3例X连锁多内分泌腺病肠病伴免疫失调(IPEX)综合征患儿的临床特点及基因变异情况。方法总结复旦大学附属儿科医院2013年1月24日至2019年7月29日收治的3例IPEX综合征患儿的临床特点、实验室检查与基因检测的结果、治疗及预后的情况。结果 3例患儿均于婴幼儿期起病, 其中1例以糖尿病伴酮症酸中毒为首发症状, 2例以腹泻起病。3例患儿均有消化道受累的表现, 其中1例经内镜及病理检查诊断为极早发炎症性肠病。3例患儿中有2例合并内分泌腺受累, 其中1例表现为1型糖尿病伴甲状腺球蛋白及甲状腺过氧化物酶抗体阳性, 但随访未发现甲状腺功能异常;另1例表现为甲状腺功能低下, 予左旋甲状腺素治疗。3例患儿均携带FOXP3基因错义变异, 包括c.1222G>A(p.V408M)、c.767T>C(p.M256T)和c.1021A>G(p.T341A)。1例经异基因造血干细胞移植治疗后症状缓解, 1例予生物制剂加胰岛素治疗后病情稳定, 另1例出生后3个月因难治性脓毒性休克及多器官功能衰竭夭折。结论 FOXP3基因变异相关的IPEX综合征可能具有起病早、临床表现多样的特点。对...     

肺结核并糖尿病的临床比较研究

目的了解肺结核合并糖尿病的相互影响、临床表现、治疗和预后．方法对同期的60例肺结核并糖尿病患者（A组）与66例单肺结核患者（B组），以同一方案治疗，比较两组的临床症状、胸部X线表现、实验室检查及治疗效果．结果A组临床症状较严重，病变以渗出、干酪病灶为主，范围广，痰菌阳性率高，进展快．A组痊愈率、好转率、痰菌阴转率均低于B组．结论及时控制血糖水平、加强抗痨治疗有助于改善糖尿病合并肺结核患者的预后．     

CLCNKB基因在经典型Bartter综合征发病机制中的作用

Bartter综合征是一种以低钾性碱中毒、高肾素-血管紧张素-醛固酮血症等为特征的遗传代谢性疾病。经典型Bartter综合征是Bartter综合征的常见类型,主要由编码位于基底膜侧的电压门控氯离子通道蛋白ClC-Kb的CLCNKB基因变异所致。该病各年龄段均可发病,主要见于儿童期,临床表现多变,从严重到非常轻微。本文综述了经典型Bartter综合征致病基因CLCNKB及其编码蛋白ClC-Kb的结构与功能,阐释了CLCNKB可能的变异机制,回顾了中国人群CLCNKB基因变异情况并对基因型-表型的相关性进行简单阐述。     

The role of cyclooxygenases and prostanoid receptorsin furosemide-like salt losing tubulopathy: the hyperprostaglandin E syndrome

Hyperprostaglandin E syndrome/antenatal Bartter syndrome is characterized by NaCl wasting and volume depletion, juxtaglomerula hypertrophy, hyperreninism and secondary hyperaldosteronism. Primary causes are mutations in the gene for Na-K-2Cl-cotransporter, NKCC2, or for potassium channel, ROMK, responsible for medullary NaCl malabsorption. Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture of the patients. Therefore the term hyperprostaglandin E syndrome has been introduced. It is unclear how prostaglandins aggravate the NaCl transport deficiency. Aspects to prostaglandin synthesis and receptor-mediated function within the kidney in patients suffering from hyperprostaglandin E syndrome/antenatal Bartter syndrome will be discussed.     

The role of cyclooxygenases and prostanoid receptorsin furosemide‐like salt losing tubulopathy:the hyperprostaglandin E syndrome

Hyperprostaglandin E syndrome/antenatal Bartter syndrome is characterized by NaCl wasting and volume depletion, juxtaglomerula hypertrophy, hyper‐reninism and secondary hyperaldosteronism. Primary causes are mutations in the gene for Na‐K‐2Cl‐cotransporter, NKCC2, or for potassium channel, ROMK, responsible for medullary NaCl malabsorption. Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture of the patients. Therefore the term hyperprostaglandin E syndrome has been introduced. It is unclear how prostaglandins aggravate the NaCl transport deficiency. Aspects to prostaglandin synthesis and receptor‐mediated function within the kidney in patients suffering from hyperprostaglandin E syndrome/antenatal Bartter syndrome will be discussed.     

Hypothesis: SLC12A3 Polymorphism modifies thiazide hypersensitivity of antenatal Bartter syndrome to thiazide resistance

We report a 5-year-old boy with thiazide-resistant Bartter syndrome. This is highly unusual since thiazide hypersensitivity is a common diagnostic finding in Bartter syndrome patients. Subsequent molecular testing identified compound heterozygosity for two novel mutations in KCNJ1, (c.556A > G and c.683G > A) which is associated with Bartter syndrome, and a paternally inherited polymorphism in SLC12A3 (c.791G > C). Mutations in SLC12A3 cause the thiazide-resistant tubulopathy Gitelman syndrome. Based on published studies of this polymorphism in SLC12A3 and the features of the proband's father, we postulate that this polymorphism modifies the phenotype of Bartter syndrome in the proband to thiazide resistance.     

Prenatal diagnosis of MAGED2 gene mutation causing transient antenatal Bartter syndrome

Transient antenatal Bartter syndrome due to melanoma-associated antigen D2 gene mutation is a newly reported type of Bartter syndrome. Its characteristics include an X-linked inheritance pattern, early-onset hydramnios, and spontaneous disappearance of symptoms after childbirth. To date, there have been no reports of prenatally diagnosed cases. We herein present the case of a preterm male born to a mother with early-onset hydramnios and a family history of X-linked idiopathic hydramnios. We suspected melanoma-associated antigen D2 gene mutation and performed direct sequencing. As a result, we were able to prenatally establish a diagnosis of transient Bartter syndrome due to a melanoma-associated antigen D2 gene mutation.     

An asymptomatic chronic hypokalaemia

We report the case of an asymptomatic patient presenting a severe chronic renal hypokalaemia. Once being sure of no diuretics use, two hypothesis can be mentioned for a normotensive patient presenting an hypokalaemia associated with a metabolic alcalosis: Bartter syndrome or Gitelman syndrome. The highlighting of low magnesaemia and hypocalciuria strongly concentrates the diagnosis on Gitelman syndrome. First, this has been strengthened by the results of renal function tests and later it has confirmed by molecular diagnosis with the identification of a known homozygous mutation on SLC12A3 gene. In the patient family, the same chromosomal abnormality has been found in the young sister. For these two patients the treatment ordered is an antikaliuretic diuretic, magnesium and potassium supplements. This case shows the difficulty to diagnose Gitelman syndrome: it is frequently mistaken for Bartter syndrome. The main differences between these two syndromes are magnesaemia and calciuria. Furthemore , patients with Gitelman syndrome are often asymptomatic, this explains why prevalence of this illness is probably underestimated.     

Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome

Yu Y, Xu C, Pan X, Ren H, Wang W, Meng X, Huang F, Chen N. Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome. Mutations in the gene CLCNKB encoding the ClC‐Kb chloride channel causes classic Bartter syndrome, which is characterized by hypokalaemic metabolic alkalosis, renal salt loss, hyper‐reninaemic hyperaldosteronism and normal blood pressure. We aimed to investigate the underlying mutations in CLCNKB in two Chinese patients with classic Bartter syndrome and then test the effect of the mutations on ClC‐Kb chloride channel activity. Mutation analysis of CLCNKB was performed by polymerase chain reaction (PCR) direct sequencing. Expression of the wild‐type and mutant ClC‐Kb was heterologous in Xenopus laevis oocytes. We identified three novel CLCNKB gene mutations, including one homozygous missense mutation (R351W) in one patient and two compound heterozygous mutations (R30X and A210V) in the other. As determined by two‐electrode voltage‐clamp analysis of ClC‐Kb channel activity, R30X abolished the current amplitude; A210V and R351W significantly reduced the current amplitude. A210V was almost as sensitive as the wild type to extracellular pH and calcium, whereas R351W removed extracellular calcium activation and markedly reduced alkaline pH activation of ClC‐Kb. The three novel CLCNKB mutations we identified in two Chinese patients with classic Bartter syndrome have a role in altering the functional properties of ClC‐Kb channels.     

Heterozygous mutations of the gene for Kir 1.1 (ROMK) in antenatal Bartter syndrome presenting with transient hyperkalemia,evolving to a benign course

Bartter-like syndrome encompasses a set of inherited renal tubular disorders associated with hypokalemic metabolic alkalosis, renal salt wasting, hyperreninemic hyperaldosteronism, and normal blood pressure. Antenatal Bartter syndrome, a subtype of Bartter-like syndrome, is characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Mutations in the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and ATP-sensitive inwardly rectifying potassium channel (ROMK) of the thick ascending limb of Henle's loop have been identified in the antenatal Bartter syndrome. We report the identification of two heterozygous mutations of the gene for Kir 1.1 (ROMK) from an antenatal Bartter syndrome patient who presented at birth with mild salt wasting and a biochemical findings that mimicked primary pseudohypoaldosteronism type 1, such as hyperkalemia and hyponatremia, and evolved to a relatively benign course. We have identified amino acid exchanges Arg338Stop and Met357Thr in the gene exon 5 for ROMK by PCR and direct sequencing. Both mutations alter the C-terminus of the ROMK protein, and can affect channel function.     

Sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition

Sclerochoroidal calcification is an uncommon condition. Metabolic evaluation and clinical examination are important to exclude associated systemic conditions such as the Bartter and Gitelman syndromes. It has been suggested that the lesions seen in sclerochoroidal calcification are calcium pyrophosphate dihydrate crystals. This report describes the first documented case in the UK of sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition.     

Inheritance of Bartter syndrome

The Bartter syndrome is regarded as an autosomal recessive trait because of sib occurrence, equal sex ratio, and normal parents. Recently, obligatory carriers were shown to have the same pattern of platelet aggregation inhibition as their affected children, possibly a reflection of altered prostaglandin action. We investigated eight patients, and their parents and sibs, and found that all persons included in the study had impaired thrombocyte aggregation. These aggregation studies support the hypothesis that the Bartter syndrome is an autosomal recessive trait.