90例肾小管性酸中毒临床分析

为提高对肾小管性酸中毒(RTA)的临床认识，减少误诊和漏诊，回顾性分析了90例RTA的病因、临床症状、体征和实验室检查。结果发现原发性RTA占65．6％，继发性RTA占34．4％，临床初次误诊高达54．4％。RTA临床表现无特异性，生长发育落后最常见，占72．2％，其中6例合并生长激素缺乏(GHD)，其他表现有纳差、呕吐、下肢疼痛、骨骼畸形等。临床分型中I型最常见，占82％，Ⅱ、Ⅲ型各占6．7％，Ⅳ型为4．6％。检测尿酸化功能66例，其中I型达印例，52例明显下降，8例轻度下降者经NH4Cl负荷试验确诊。提示RTA在儿童期并非罕见，临床误诊率高，需提高警惕；多种疾病可继发RTA，临床上应全面判断；尿酸化功能测定是RTA诊断的可靠指标。     

Medullary sponge kidney associated with distal renal tubular acidosis in a 5-year-old girl

Introduction Medullary sponge kidney (MSK) is characterized by cystic dilatation of the inner medullary collecting ducts, which causes the kidneys to resemble a sponge.Case report Although distal renal tubular acidosis (dRTA) is commonly observed in patients with MSK, we report a 5-year-old girl with MSK who had features of both dRTA (nephrocalcinosis, hypercalciuria, hypocitraturia) and proximal tubular dysfunction (hyperuricosuria, impaired tubular phosphate reabsorption and proteinuria).Discussion Metabolic acidosis, hypercalciuria, hypocitraturia, tubular phosphate reabsorption and growth retardation in the patient improved with alkali therapy.     

Evaluation of renal tubular acidosis

Renal tubular acidoses (RTA) comprises of a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. The RTAs are classified into chiefly three types (types 1,2 and 4) based on clinical and laboratory characteristics. Correct diagnosis involves careful evaluation, including exclusion of other entities causing acidosis. A variety of tests are required to be administered in a stepwise fashion for the diagnosis and characterization of RTA.     

以肾小管酸中毒为首发表现的儿童恶性淋巴瘤

原发性肾淋巴瘤是原发于淋巴结以外的一种恶性淋巴瘤,罕见于儿童。该文报道2例以肾小管酸中毒为首发表现,以肾组织穿刺病理确诊的儿童原发性肾淋巴瘤。2例皆以“多饮、多尿、乏力、呕吐、贫血”为主要症状,双肾肿大,伴低钾、低钙、低磷,代谢性酸中毒等。1例放弃治疗,另外1例经泼尼松、长春新碱、阿糖胞苷＋L-天冬氨酰胺酶(PVA+L-ASP)方案化疗,联合氨甲喋呤、地塞米松、阿糖胞苷鞘内注射、纠酸、补钾、输血及对症支持治疗后,多饮多尿症状缓解,内环境稳定, 复查肾B超无异常发现。一旦怀疑该型恶性淋巴瘤,应尽快肾组织穿刺病理确诊,早期采取综合治疗,包括手术、化疗与放疗、支持疗法等。     

远端肾小管酸中毒患儿基因型及临床表型的相关性分析

目的对确诊的6例原发性远端肾小管酸中毒(dRTA)的病例行基因型及临床表型的相关性分析。方法对2017年11月至2019年8月确诊于华中科技大学同济医学院附属武汉儿童医院的6例dRTA患儿行病史资料采集及相关辅助检查,评估其生长发育情况,留取静脉全血进行Trio全外显子高通量测序,经全谱遗传病精准诊断云平台系统分析筛选和数据分析,对可疑突变进行Sanger测序验证,后应用蛋白预测软件进行蛋白功能预测。结果6例患儿的临床症状、体征和辅助检查均符合dRTA的诊断,均表现为生长发育落后,1例患儿出现X型腿,1例患儿出现骨质疏松。辅助检查均提示低钾血症、代谢性酸中毒、碱性尿,3例患儿出现肾脏钙质沉着,2例患儿出现肾脏结石,所有患儿的父母亲均无临床表型。1例患儿为SLC4A1基因纯合突变[c.2102(exon17)G>A,p.G701D],为既往报道的常染色体隐性遗传高频突变位点,该患儿同时合并dRTA及溶血性贫血;3例为SLC4A1基因杂合突变,均为De novo突变[c.1766(exon14)G>A,p.R589H,c.1765(exon14)C>T,p.R589C],为既往报道的常染色体显性遗传高频突变位点,确诊年龄与肾脏影像学异常存在相关性。1例为ATP6V1B1基因复合杂合突变[c.806(exon9)C>T,p.P269L;c.1153(exon12)C>A,p.P385T],均为未见文献报道的新突变位点。1例为ATP6V0A4基因纯合无义突变[c.1899C>A,p.Y633X,208],为未见文献报道的新突变位点。结论SLC4A1、ATP6V1B1、ATP6V0A4是目前已明确的dRTA的主要致病基因,其突变特点及遗传方式与临床表型相关。基因检测可以对可疑的dRTA患者行早期分子诊断,有助于临床表型的筛查及个体化治疗。     

Genetic and long-term data on a patient with permanent isolated proximal renal tubular acidosis

A 12-year-old girl presented with permanent isolated proximal renal tubular acidosis (pRTA), glaucoma, band keratopathy, mild cataract and short stature. Severe metabolic acidosis was caused by the impairment of bicarbonate reabsorption in the proximal tubules and alkali therapy improved her acidaemia. A homozygous G to A transition at nucleotide 1,678 in the basolateral kidney type Na⁺/HCO₃ ⁻ (kNBC) co-transporter gene SLC4A4, which is critical in HCO₃ ⁻ resorption in renal proximal tubules, was identified. Her height and height velocity (HV) were very low (−4.0 SD and −4.4 SD, respectively) before alkali treatment, but both improved after initiating alkali therapy at the age of 2 years and 3 months. The patient's body height and HV were 131.5 cm (−2.7 SD) and 4.0 cm (−2.0 SD), respectively at the age of 12 years. Conclusion This case demonstrates that early administration of alkali therapy and sustained correction of acidosis, even if inadequate to correct the metabolic acidosis, can markedly improves growth in permanent isolated proximal renal tubular acidosis. Received: 3 April 2000 / Accepted: 5 July 2000     

SLC4A1 复合杂合突变致遗传性球形红细胞增多症并远端肾小管酸中毒1 例报告并文献复习

目的分析SLC4A1复合杂合突变致遗传性球形红细胞增多症(HS)并远端肾小管酸中毒(dRTA)的临床表型与基因变异的关系。方法回顾分析1例确诊HS合并dRTA患儿的临床资料,以及患儿及父母外周血全外显子测序及Sanger验证结果。结果男性患儿,1岁7个月,主要临床表现为输血依赖性球形红细胞增多、代谢性酸中毒、低钾血症及生长发育迟缓。检测到患儿SLC4A1 基因2个已报道的错义变异c.2102GA p.(Gly701Asp),c.1988TC p.(Met663Thr),分别来源于父母。结论经基因检测确诊由SLC4A1复合杂合变异所致的遗传型HS合并dRTA,符合常染色体隐性遗传。     

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??Objective??To analyze the clinical features and the results of genetic diagnosis in children with hypokalemic renal tubular diseases. Methods??The clinical data of 38 patients with hypokalemic renal tubular diseases were analyzed retrospectively??who were treated in Children’s Hospital Affiliated to Shanghai Jiao Tong University from Jan. 2010 to Jan. 2016. Results??Totally 38 patients with hypokalemic renal tubular diseases were enrolled in this study. There were 18 cases of renal tubular acidosis??RTA?? including 17 cases of type??RTA and 1 case of type?? RTA. There were 11 cases of Bartter syndrome??5 cases of Gitelman syndrome and 4 cases of Fanconi syndrome. The common clinical manifestations of hypokalemic renal tubular diseases included myasthenia??nausea??vomiting??polydipsia??polyurine and growth retardation. One case of Fanconi syndrome progressed to chronic Kidney disease??phase ????while the other
children had normal renal function. Glomerular proteinuria was found in 1??1 and 3 children with Bartter syndrome??Gitelman syndrome and Fanconi syndrome??respectively. Additionally??1 case with Fanconi syndrome has tubular proteinuria. However??urinary trace proteins associated with glomerular and tubular injury commonly elevated in these hypokalemic renal tubular diseases. Genetic analysis showed a new potential heterozygous mutations of ATPV0A4 in type??RTA and three heterozygous mutations of SLC12A3 in Gitelman syndrome. Conclusion??The clinical symptoms vary in patients and are featured mainly by myasthenia??nausea??vomiting??polydipsia??polyurine and growth retardation. Glomerular and tubular injuries are commonly found in hypokalemic renal tubular diseases. Moreover??genetic diagnosis may be helpful in diagnosis??treatment and genetic counseling.     

Chronic active hepatitis with renal tubular acidosis presenting as hypokalemic periodic paralysis with respiratory failure

A child with chronic active hepatitis and renal tubular acidosis, presenting with periodic hypokalemic paralysis resulting in respiratory failure, is described.     

Type 4 renal tubular acidosis (subtype 2) in a patient with methylmalonic acidaemia

A 10-month-old male infant with vitamin B₁₂ non-responsive methylmalonic acidaemia is reported. Laboratory results revealed hyperkalaemic, hyperchloraemic, metabolic acidosis with slight azotaemia. The urinary pH decreased (below 5.5) to compensate for acidaemia. Levels of plasma renin activity and plasma aldosterone concentration were low. The renal biopsy showed tubulo-interstitial nephritis. We suggested the diagnosis of type 4 renal tubular acidosis, subtype 2, i.e. hyporeninaemic hypoaldosteronism. We suggest that chronic renal disease may be a common complication of methylmalonic acidaemia.     

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。     

Renal calculi in children

An increasing number of paediatric patients of all ages with renal calculi are being seen in outpatient clinics worldwide. This is attributed to changes in environmental factors like diet, fluid intake and obesity. In children however, genetic and/or metabolic disorders are still the main reason for kidney stones. Next to hypercalciuria, which is generally considered to be the most frequent risk factor, other lithogenic or stone-inhibitory disorders like hypocitraturia or hyperoxaluria and a variety of renal tubular diseases have to be evaluated by urine and/or blood analysis. Non-specific symptoms like growth retardation, intestinal malabsorption or bone demineralization are to be considered not only to avoid further complications, but for diagnostic purposes. In preterm infants a high incidence of nephrocalcinosis is observed. These infants often have a combination of immature kidney function or medication that leads to relative hypocitraturia. Concise evaluation to diagnose the underlying patho-mechanism as early as possible is mandatory in all paediatric patients. In more than three-quarters of children a metabolic basis of urolithiasis/nephrocalcinosis will be found. Early treatment by reducing urinary saturation index by increasing fluid intake, by providing crystallization inhibitors, but also by disease specific medication prevents recurrent kidney stones and/or progressive nephrocalcinosis and therefore deterioration of renal function.     

ATP6V0A4基因变异致新生儿远端肾小管酸中毒1例报告及5年随访结果

目的 分析新生儿远端肾小管酸中毒(DRTA)的基因型、临床特点及远期发育情况.方法 回顾分析1例DRTA患儿的临床资料.结果 足月顺产女婴,生后体质量不增、睡眠差、哭闹、轻度脱水等.多次血气分析提示严重的高氯性酸中毒、低钾血症,碱性尿液,肾脏钙质沉着.高通量基因测序显示患儿ATP6V0A4基因有复合杂合变异,分别是来自...     

Idiopathic Hypercalciuria in Children

ABSTRACT. Between 1981 and 1983, 49 children aged 2 to 15 years were diagnosed as having idiopathic hypercalciuria (IH). They were divided into 3 groups based on their response to dietary manipulation: group I (32/49) had absorptive hypercalciuria; group II (8/49) had renal hypercalciuria and group III (6/49) had sodium-dependent hypercalciuria. Response to diet was more reliable than Pak's test in differentiating between the three groups. A control group (CG) of 45 healthy, age matched children determined baseline levels for all metabolic parameters. At the time of presentation IH children did not differ from the CG in height or weight. Fifty percent of IH children had first degree relatives with urolithiasis. Yet, only 16% of the IH children had urolithiasis, the majority presenting with gross hematuria and urinary tract infections (UTI). With few exceptions the clinical symptoms resolved when urine calcium excretion was controlled. Severe calcium restriction in a few patients produced osteoporosis and delayed bone age although growth velocity was unaffected. Thiazide therapy in a few patients produced some metabolic derangements. The authors conclude that IH in childhood is a benign disease which may present with UTI or hematuria. They further propose a new classification method based on response to dietary manipulation.     

Renal magnesium wasting,incomplete tubular acidosis,hypercalciuria and nephrocalcinosis in siblings

Polyuria, hyposthenuria, hypomagnesemia, hypercalciuria, advanced nephrocalcinosis, low citrate excretion and low glomerular filtration rates were observed in two female siblings who were followed over 10 years. Acid loading revealed incomplete distal tubular acidosis. Hypomagnesemia was due to renal magnesium wasting. It is suggested that the defect in tubular transport of magnesium is an important factor in the pathogenesis of this syndrome.Supported by the German Research Foundation within the SFB 90 Cardiovaskuläres System and grant Lo/260/1Dedicated to Prof. Dr. H. Bickel on the occasion of his 60th birthday     

Growth hormone stimulation tests in chronic renal failure with metabolic acidosis

Metabolic acidosis is one of the possible causes of growth retardation in chronic renal failure (CRT³'). Data about the effect of metabolic acidosis on growth hormone (GH) secretion in CRF are limited. A study was earned out on eight CRF patients, hospitalized because of severe metabolic acidosis, and eight age-matched prepubertal healthy short children. Growth hormone stimulation tests were done with L-dopa and clonidine before or during acidosis therapy and after the correction of metabolic acidosis. The levels of GH were measured by radio-immunoassay. The mean of the peaks of both tests were used for each patient and statistical significance was tested by Mann-Whitney U and Wilcoxon tests. No difference was found between the GH peaks of the two groups during acidosis and after the correction of acidosis (Wilcoxon test, P > 0.05). In view of this data it was concluded that metabolic acidosis has little effect on GH stimulation tests.     

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L⁻¹ of urine (range: 0.17–546.31 pmol/L⁻¹. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary β 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.