Hypokalaemia and failure to thrive: report of a misleading onset

Aim: We report a case of Gitelman Syndrome (GS) in a 9‐year‐old girl, previously diagnosed as a Bartter syndrome at one year of life. Methods: She had been treated with potassium, for over 8 years and was admitted because of fatigue, numbness and weakness of both legs. The patient has typical laboratory findings, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria, thus GS was suspected. Results: Genetic analysis was performed two mutations IVS9(+1)G>T were detected in the thiazide‐sensitive Na‐Cl cotransporter (TSC) gene (SLC12A3), thus she was diagnosed as having GS. She was treated with oral potassium and magnesium supplements with resolution of the symptoms. Conclusion: This case reminded us that doctors should be alert to the initial presentation of renal tubular diseases. Detailed electrolyte analysis, hormone evaluations and clinic follow‐up are mandatory for their correct differential diagnosis.     

Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions

We describe two girls with atypical presentations of multisystem disorders due to deletions in mitochondrial DNA (mtDNA). One presented with painful carpopedal spasms due to hypoparathyroidism at the age of 4 years. The disease was rapidly progressive with development of truncal and limb ataxia, spastic paraparesis, muscle weakness and wasting, pigmentary retinal degeneration and sensorineural hearing loss. She had short stature and vitiligo patches, hirsutism, anaemia, diabetes mellitus and exocrine pancreatic dysfunction. The other girl presented at the age of 6 years with polydipsia, polyuria and fatigue due to renal tubular dysfunction. The disease was insidiously progressive with poor growth and development of sensorineural hearing loss, muscle weakness and truncal and limb ataxia. Morphological, enzyme histochemical and biochemical investigations indicated mitochondrial dysfunction of skeletal muscle, liver and kidney in one patient and of skeletal muscle and liver in the other. Both patients had large proportions of mtDNA molecules with deletion in liver, kidney, skeletal muscle and blood cells.Conclusion It may be concluded that symptoms from several different organs may be the first manifestation of a mtDNA deletion disorder.     

Treatment for nocturnal enuresis: The current state in Japan

Nocturnal enuresis is common problem in children with a prevalence as high as 20% among children aged 5. Though nocturnal enuresis does not directly impose imminent danger to a patient's life, children with enuresis and their parents can be psychologically suffering in day‐to‐day life, including in school activities. Therefore, it is important to provide an explanation regarding the cause of nocturnal enuresis, how to approach the disorder, the course, and the outlook leading to the planned treatment. The cause of enuresis is considered to be a mismatch between nocturnal diuresis and nocturnal bladder capacity, nocturnal polyuria due to a lack of circadian change in antidiuretic hormones, and a developmental delay in the voiding mechanisms. Therefore, patients can be classified as the type associated with a large amount of urine at night (polyuria type), the type that is associated with a functionally small bladder capacity (bladder type), the type associated with both the aforementioned (mixed type), or the type that does not fall under any of these (normal type). Based on this logic, although the International Children's Continence Society has issued the standardization document, in which the enuresis alarm and desmopressin therapy are recommended as the first line treatment, a different tack has been taken in Japan, where the therapeutic strategy is plotted depending on the type of enuresis; pharmacotherapy for enuretic children aged 6 years or older includes desmopressin acetate for polyuria type, anticholinergic agents for bladder type, and a combination of these agents for mixed type.     

Nocturnal enuresis

Childhood enuresis is a common socially disruptive problem. The possible pathophysiological factors include a disorder of sleep arousal, nocturnal polyuria, and low bladder capacity. The evaluation of a patient with nocturmal nuresis is aimed to exclude any organic pathology, UTI and voiding dysfunction. An approach to management of this common disorder is outlined.     

Social and behavioural perspectives in enuretics, former enuretics and non-enuretic controls

Social and behavioural traits in children with primary nocturnal enuresis were compared with children who had outgrown their enuresis and children who had never bed-wetted after three years of age. The study group included 14 children with primary nocturnal enuresis, 15 children who had had primary nocturnal enuresis and 15 age- and sex-matched controls. The mothers of all children were interviewed using a 32-item questionnaire. If primary nocturnal enuresis were a neurotic disease, we would have expected a higher frequency of emotional dysfunction in children with enuresis and an increase in the symptoms or symptom substitution when bed-wetting was resolved. No significant differences in emotional or behavioural traits among the three groups were found. We conclude that children with primary nocturnal enuresis were well adjusted individuals and display similar social and behavioural traits as their peers. This study lends further support to the theory that primary nocturnal enuresis is not a psychological disorder.     

原发肾小管性低钾碱中毒的临床特点

目的 探讨原发肾小管性低钾碱中毒的临床特点.方法 收集在天津市儿童医院住院治疗的原发肾小管性低钾碱中毒患儿8例,其中Bartter综合征(BS)、Gitelman综合征(GS)各4例.回顾性分析其临床表现、实验室检查、治疗方法及转归情况.结果 4例BS均婴幼儿期起病,临床表现为间断呕吐、腹泻、脱水、生长发育迟缓.4例GS发病年龄为10～15岁,临床表现为肢体无力、四肢麻木及间断手足搐搦.8例患儿血压均正常.实验室检查均表现为低血钾、代谢性碱中毒、尿钾、尿氯排出增加;4例BS息儿血浆肾素、血管紧张素、醛固酮明显升高;4例GS患儿血管紧张素均升高,血浆肾素升高3例、醛固酮明显升高2例;BS患儿尿钙肌酐比>0.2,GS患儿伴低血镁、尿钙肌酐比<0.2.2例BS患儿B超示双肾回声均匀增强,其中1例左肾盂扩张.单纯补钾或联合补镁、吲哚美辛、螺内酯和卡托普利后症状缓解.结论 原发肾小管性低钾碱中毒主要表现为低血钾、代谢性碱中毒、血压正常.检查其血镁、尿钾、尿氯、尿钙肌酐比和血浆肾素、血管紧张素、醛固酮水平可帮助诊断.BS和GS的发病机制、临床表现、治疗及预后均有不同.     

DDAVP and urine osmolality in refractory enuresis.

A double blind crossover trial of 20 micrograms intranasal 1-deamino-8-d-arginine vasopressin (DDAVP) versus placebo was carried out in 17 children with intractable enuresis aged between 6 and 13 years who had failed to respond to drugs and an enuresis alarm. Fluid intake was not restricted. There was a significant reduction in the number of wet nights. Seven children (41%) were cured or showed considerable improvement, with strong evidence against any placebo effect. The best response was seen in children aged 10 years or over and if urine osmolality after DDAVP reached beyond 1000 mmol/kg or was already at this concentration. The degree of overnight rise in urine osmolality after treatment with DDAVP was not predictable but correlated well with the clinical improvement in nocturnal diuresis present in eight of the children. A further 12 children with equally refractory enuresis were given 20 micrograms of the active drug to take during their school journeys or holidays. Six of them had previously normal overnight urine osmolalities with only two successes, but of the six who had nocturnal diuresis before treatment, five became dry, suggesting that DDAVP acts largely by anti-diuresis and might be most useful in children with nocturnal polyuria.     

Isolated Neurosarcoidosis Revealed by Diabetes Insipidus,Visual Loss and Diplopia in a Child Patient: A Diagnostic Problem

We report a case of 15-yr-old child that was presented with headache, polyuria, polydipsia, recent ocular motor and abducens nerve palsies and rapid visual loss. He had a long history of progressive symmetric muscular weakness predominant in the lower limb girdle. Water deprivation revealed central diabetes insipidus. Hormonal explorations demonstrated preserved pituitary function with mild hyperprolactinemia at 21.5 ng/ml (N: 2.6 to 13.1 ng/ml). Magnetic resonance imaging showed an extensive isosignal T1 and hyposignal T2 enhanced lesion infiltrating the pituitary gland, optic-chiasmal hypothalamic region, cavernous sinus, cerebrum tent and sphenoid and temporal meningeal spaces. The serum level of angiotensin converting enzyme and cerebrospinal fluid analysis were normal. No other systemic localisation was identified. Muscle biopsy objectified dystrophic changes. Genetic study identified a delT 521 mutation characteristic of Limb-girdle muscular dystrophy type 2C. Corticotherapy rapidly ameliorated the neurological symptoms. This patient was diagnosed as having neurosarcoidosis. Neurosarcoidosis is rarely reported in childhood. We discuss the problems related to diagnosis in such a situation below.     

Mutations in the chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype

Gitelman syndrome is an inherited renal disorder characterized by impaired NaCl reabsorption in the distal convoluted tubule and secondary hypokalemic alkalosis. In clinical practice, it is distinguished from other hypokalemic tubulopathies by the presence of both hypomagnesemia and normocalcemic hypocalciuria. To date, only mutations in a single gene encoding the thiazide-sensitive NaCl cotransporter have been found as the molecular basis of GS. We describe three unrelated patients presenting with the typical laboratory findings of GS. Mutational analysis in these patients revealed no abnormality in the SLC12A3 gene. Instead, all patients were found to carry previously described mutations in the CLCNKB gene, which encodes the kidney-specific chloride channel ClC-Kb, raising the possibility of genetic heterogeneity. Review of the medical histories revealed manifestation of the disease within the first year of life in all cases. Clinical presentation included episodes of dehydration, weakness, and failure to thrive, much more suggestive of classic Bartter syndrome than of GS. The coexistence of hypomagnesemia and hypocalciuria was not present from the beginning. In the follow-up, however, a drop of both parameters below normal range was a consistent finding reflecting a transition from cBS to GS phenotype. The phenotypic overlap may indicate a physiologic cooperation of the apical thiazide-sensitive NaCl cotransporter and the basolateral chloride channel for salt reabsorption in the distal convoluted tubule.     

McArdle's disease in childhood: report of a new case.

McArdle's disease (glycogenosis type V) is an inherited glycogen storage disease characterized clinically by myalgia, cramps and sometimes myoglobinuria, triggered by exercise. The onset of exercise intolerance is usually in late childhood or adolescence and diagnosis is exceptionally established during infancy. We report the case of a 6-year-old girl who had been complaining of aching muscles for a long time, and who presented after a near-drowning incident, with extensive muscle necrosis, probably secondary to myophosphorylase deficiency-induced cramps. These unusual manifestations led to the diagnosis of this rare disorder. We compare the clinical findings of this case to nine previous reports. This highlights the heterogeneous spectrum of this disease in childhood and supports the distinction of three clinical pictures in childhood: a neonatal form rapidly fatal, a milder form with congenital myopathic symptoms and a benign classical form with myalgia, cramps and pigmenturia.     

Aldosterone-producing adenoma presenting with hypokalemic myopathy. Case report and review

A 9-year-old boy who complained of fatigue, myalgias, and progressive weakness was found to have a markedly elevated serum creatine phosphokinase (CPK). He developed polyuria with polydipsia and was noted to be hypertensive and severely hypokalemic. Treatment with potassium and spironolactone alleviated his signs and symptoms and normalized the blood pressure and CPK. Initial studies revealed low plasma renin activity that did not increase with change from supine to upright position. Plasma aldosterone was consistently elevated in the supine position, decreased with upright posture, and was not suppressed by administration of dexamethasone. Plasma 18-hydroxycorticosterone also was elevated. Enhanced computerized tomography (CT) revealed a mass in the left adrenal that had not been seen on the initial unenhanced scan. Adrenal vein catheterization confirmed elevated plasma aldosterone on that side. Adrenalectomy was performed, and a well-encapsulated adenoma was found at examination of the surgical specimen. Postoperatively, suppression of plasma renin activity continued for many months without signs of aldosterone deficiency.     

基于调查问卷的中国城市小学生遗尿患病率及其生活质量状况

目的 调查中国小学生夜间遗尿患病率及其与生活质量的关系。方法 研究数据来源于全国城市学龄儿童睡眠状况研究,抽样方法为多级随机整群抽样。 发放问卷23 791 人,21 755人返回的问卷符合质量控制要求。采用描述性统计分析中国小学生遗尿的患病率;以是否遗尿为因变量,《儿童一般生活质量评估调查问卷》25个条目为自变量,建立Logistic回归方程,分析遗尿与非遗尿儿童生活质量各条目的差异。结果 中国小学生遗尿患病率为4.6%,调查的9个城市遗尿患病率以武汉最高（7.4%）,上海最低（3.3%）。中国小学生遗尿男女生之比为1.51∶1。Logistic回归方程显示,遗尿与常常被人责骂（除父母、老师外）、常常伤害他人、常常生病和常常被老师责骂等生活质量因子具有正性关系;遗尿与通常有很多好朋友、常常帮助他人、通常认为父母是爱他的和通常用功学习等生活质量因子具有负性关系。结论 基于问卷调查的中国小学生遗尿患病率为4.6%,遗尿与儿童生活质量中环境状态有密切的关系。     

Prepulse inhibition of startle, intelligence and familial primary nocturnal enuresis

Previous studies have shown a significant reduction of prepulse inhibition of startle in boys with primary nocturnal enuresis. Those enuretic boys who had higher IQs showed less prepulse inhibition. This study evaluates the association of prepulse inhibition and IQ in primary nocturnal enuresis in respect to family history of primary nocturnal enuresis. Prepulse inhibition of startle was studied in 83 boys with primary nocturnal enuresis and 57 non-enuretic boys using an interval of 120 ms between the onset of a 75 dB 1000 Hz tone and a 104 dB noise burst. Of the boys with primary nocturnal enuresis, 56 had a family history of primary nocturnal enuresis and 27 had no family history (no first-degree relative). Of the 57 non-enuretic boys, 42 also had no family history (no first-degree relative) of primary nocturnal enuresis, while 15 did have a positive family history. Associations between prepulse inhibition and IQ scores were compared among these four groups. Strong and significant associations between prepulse inhibition deficit and higher IQ scores in the enuretic group with familial primary nocturnal enuresis were unique in comparison to the other groups. Conclusions: The strong heritabilities of primary nocturnal enuresis, intelligence and prepulse inhibition suggest genetic mediation of the association of prepulse inhibition with intelligence in familial primary nocturnal enuresis.     

Epidemiology of childhood nocturnal enuresis in Malaysia

OBJECTIVES: To estimate the prevalence of nocturnal enuresis in primary school children in Malaysia and to determine the factors associated with primary nocturnal enuresis. METHODS: This was a cross-sectional survey. A total of 3371 self-administered questionnaires were distributed to parents of children aged 7, 9 and 12 years attending four primary schools in the city. The ICD-10 definition of enuresis was used. RESULTS: From an overall response rate of 73.8%, nocturnal enuresis was reported in 200 children (8%), primary nocturnal enuresis in 156 children (6.2%) and secondary nocturnal enuresis in 44 children (1.8%). Fifty-three percent of those with primary enuresis had a positive family history, and 54% had two or more wet nights per week. Eighty-seven percent had not sought any form of treatment despite 74% admitting to being embarrassed. Using logistic regression analysis, only three factors were significant predictors of primary nocturnal enuresis. These were: (i) younger age (P < 0.001); (ii) male sex (P < 0.033); and (iii) Indian ethnic group (P < 0.044) compared to Chinese. CONCLUSION: The prevalence of nocturnal enuresis in urban-dwelling Malaysian children is similar to that reported from Korea and Taiwan but appears to be lower than that reported from developed countries. Predictive factors associated with primary nocturnal enuresis included lower age group, male sex and Indian ethnicity.     

两例晚发型戊二酸尿症Ⅱ型患者的临床及其ETFDH基因研究

目的报道2个ETFDH基因变异导致的晚发性戊二酸尿症Ⅱ型家系的临床及遗传学特点。方法利用靶向基因捕获二代测序的方法对疑似患者及其家庭成员进行基因测序分析,回顾性分析患者的临床特点并进行文献复习。结果两个家系的先证者分别于10岁和5岁6个月发病,均以肌无力、肌肉酸痛为表现。血清肌酸激酶及其同工酶、乳酸脱氢酶均明显升高。血串联质谱分析提示多种酰基肉碱升高;尿有机酸分析发现戊二酸升高。肌电图提示肌源性损害。基因检测发现患者1的ETFDH基因存在两个新突变:c.1331TC(来自其母亲)和c.824CT(来自其父亲),其弟弟为c.1331TC突变携带者、表型正常。患者2的ETFDH基因检出一个新突变:c.177ins T,及一个已知突变:c.1474TC,分别来自其父母,其家系检出多位携带者。两例先证者均确诊为戊二酸尿症Ⅱ型,予以高剂量维生素B2治疗,症状好转。结论对于肌无力、肌肉酸痛的患者应进行肌酶、血液酯酰肉碱、尿有机酸等检测,警惕戊二酸尿症Ⅱ型的可能,基因分析有助于确诊。     

The role of sleep and arousal in nocturnal enuresis

AIM: To review what is known about the role of sleep and arousal mechanisms in the pathogenesis of nocturnal enuresis. METHODS: A review of the literature was carried out. RESULTS: The sleep of enuretic children, although polysomnographically quite normal, is exceedingly "deep"; that is enuretic children have high arousal thresholds. Apart from some overlap between enuresis and the (other) classic parasomnias, the sleep of enuretic children is no more problematic than that of the general population. Recently, the exciting possibility has arisen that the low arousability of enuretic children may be linked to the autonomous nervous system and to disturbances in the upper pons. CONCLUSIONS: Enuresis is not just a nocturnal problem but a disorder of sleep. The high arousal threshold is one of three major pathogenetic factors in enuresis-nocturnal polyuria and detrusor hyperactivity being the other two.     

SLC6A1基因变异相关儿童癫痫5例病例系列报告

背景：SLC6A1基因编码γ 氨基丁酸（GABA）转运蛋白GAT 1,该基因变异可降低GAT 1活性,影响突触间隙GABA的重摄取,在癫、智力障碍和孤独症谱系障碍等神经系统疾病的发病中起重要作用。 目的：总结SLC6A1基因变异相关儿童癫的临床表型及基因变异情况。 设计：病例系列报告。 方法：回顾性收集2007年12月至2021年10月复旦大学附属儿科医院神经科诊治的SLC6A1基因变异相关癫患儿的临床资料,总结其临床表现、治疗效果及基因检测结果,并检索文献,总结已报道SLC6A1基因变异与临床表型的关系。 主要结局指标：临床表型和SLC6A1基因突变位点。 结果：5例患儿纳入分析,男4例,女1例,起病年龄1~3岁,癫发作类型包括：肌阵挛发作4例,失神发作3例,肌阵挛 失张力发作2例,全面性强直阵挛发作1例。5例均存在精神运动发育落后,其中语言发育落后突出。随访5例患儿中4例无发作,丙戊酸单药治疗、丙戊酸联合左乙拉西坦治疗各2例。5例均携带SLC6A1基因杂合变异,且均为新发突变,其中错义变异3个,剪接变异和无义变异各1个。c.1379T>G (p.L460R)、c.1485G>A (p.W495X)尚未见报道。CAT 1蛋白胞外结构域EC3 4和跨膜区TM7是致病性或可能致病性错义变异致氨基酸改变的集中区域。 结论：SLC6A1基因变异所致癫多在幼儿期起病,癫发作类型多样,丙戊酸对其癫发作疗效好,但大多数患儿伴精神运动发育落后。新变异的发现丰富了SLC6A1基因变异谱。     

Diagnosing daytime bladder symptoms in children with nocturnal enuresis: A comparison of brief parental questionnaire with in‐depth,physician‐elicited,assessment

Aims: To assess the accuracy of brief parental questionnaire reporting of daytime bladder symptoms in children with nocturnal enuresis and compare with in‐depth reporting elicited by physician assessment, for diagnosing monosymptomatic and non‐monosymptomatic nocturnal enuresis. Methods: A cross‐sectional study of consecutive children attending an outpatient nocturnal enuresis clinic at a tertiary paediatric hospital participated in the study. Parents were asked to complete a questionnaire as part of routine assessment at their first visit which was compared with a detailed clinical assessment by the physician involving eliciting a thorough history from the parent and child. Results: Parents of 585 children participated in the study (mean age 9.2 years, range 5.0–17.5 years). Sixty percent of children were males. There was poor agreement between initial parental reporting and physician diagnosis of monosymptomatic and non‐monosymptomatic nocturnal enuresis (Kappa = 0.3, 95% confidence interval 0.21–0.37), mainly because parents underreport daytime incontinence and urgency compared with physician‐elicited information (43% vs. 69% and 66% vs. 87%, respectively). Conclusions: Parents underreport daytime symptoms by 20–25%. Reliance on a brief parental history without prompting by physicians for daytime symptoms for diagnosing type of nocturnal enuresis may be misleading and result in suboptimal management.     

Enuresis: analysis of 100 cases.

One hundred children with enuresis were studied to find out various factors responsible for this condition. Enuresis was more frequent in first born, service class and bottle fed children. There was a significant role of stress factors in causation of enuresis. We found a higher frequency of behavioral symptoms among children with enuresis. There was no significant correlation between enuresis and sex, education of parents, social class, sleep patterns, age of mother at marriage and intellectual grades of the children. Worm infestations, giardiasis, amebiasis and urinary infection were seen in 70% of cases. General body weakness, cold and nervousness were the common causes of enuresis in the parents' opinion. The main reason for not seeking the treatment at an early stage in view of parents' was that they thought enuresis a normal variant.     

遗传性远端肾小管酸中毒的临床特点和SLC4A1基因突变分析

目的研究两个原发性远端肾小管酸中毒(d RTA)家系的临床特征和致病基因SLC4A1突变情况。方法通过家系调查、病史采集和生化指标检测,分析d RTA临床表型和遗传特点。通过直接测序法检测SLC4AI基因突变。结果两个家系共有3例患者(其中两例为母子)确诊为d RTA,均有显著的临床特征,包括身材矮小、代谢性酸中毒、碱性尿、低钾血症和肾脏钙盐沉积。SLC4A1基因分析证实3例患者均存在致病性错义突变R589H(c.1766GA)。家系1的患儿为SCL4A1的新生突变,家系2患儿的SLC4A1基因突变遗传自其母,符合常染色体显性遗传特点。结论本研究首次在国内报道遗传性d RTA家系中SLC4A1基因R589H突变。对疑似遗传性d RTA患者进行基因检测可提高早期诊治率。