Renal tubular acidosis — a case report

A case of primary distal type of renal tubular acidosis (RTA) diagnosed at the age of 14 days in a neonatal nursery is reported. The course of illness and management upto the age of four years 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.     

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。     

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.     

Approach to renal tubular disorders

The renal tubule plays an important role in fluid and electrolyte homeostasis. Renal tubular disorders may affect multiple (e.g., Fanconi syndrome) or specific (e.g., nephrogenic diabetes insipidus, renal glucosuria) tubular functions. Most conditions are primary and monogenic but occasionally are secondary to other disorders (focal segmentai glomerulosclerosis, cystinosis, Lowe syndrome). Tubular dysfunction should be considered in all children with failure to thrive, polyuria, refractory rickets, hypokalemia and metabolic acidosis. Careful clinical and laboratory evaluation is essential for appropriate diagnosis and specific management of these conditions.     

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     

Nephrocalcinosis in glucose-galactose malabsorption: nephrocalcinosis and proximal tubular dysfunction in a young infant with a novel mutation of SGLT1

We report an association of proximal renal tubular dysfunction in a 50-day-old girl with glucose-galactose malabsorption who was found to have nephrocalcinosis, but no sign of nephrolithiasis. A novel homozygous nonsense mutation at 267Arg →stop (CGA→TGA) in the Na⁺-dependent glucose transporter (SGLT1) was found in loop 5 connecting transmembrane segments 6 and 7, indicating the complete loss of glucose transport activity. This case indicates that hypercalcaemia, nephrocalcinosis and proximal tubular dysfunction may be seen in association with glucose-galactose malabsorption and that most of these abnormalities improve with a glucose-galactose-free diet.     

Growth failure associated with medullary sponge kidney,due to incomplete renal tubular acidosis type 1

A girl, 12 years of age, was referred for short stature. Clinical examination and laboratory investigations currently performed in a case of growth failure gave normal results. Renal echography revealed a hyper-echogenic renal medulla. An excretory urogram showed medullary sponge kidney with bilateral renal calculi. An ammonium chloride loading test revealed a defect in acid excretion and led to the diagnosis of incomplete renal tubular acidosis. Treatment with oral bicarbonate was associated with an increase in growth velocity.     

Immunodeficiency in methylmalonic acidaemia

Three Chinese infants with methylmalonic acidaemia were described. They presented in the neonatal period with recurrent episodes of poor feeding, lethargy, apnoea and severe acidosis. The diagnosis was established by increased methylmalonic acid concentration in the plasma and/or urine. Pancytopenia was a prominent feature in all three patients. Only patient three had assessment of lymphocyte subsets and it showed diminished population of B-lymphocytes and a reversed CD4/CD8 ratio. All three patients were unresponsive to vitamin B12. They experienced severe infections including Gram-negative septicaemia, candidiasis and Pneumocystis carinii pneumonia which caused their deaths. Patients with this disease should be regarded as having severe immunodeficiency, and in addition to optimal metabolic control, they should be treated aggressively for any suspected infective episodes.     

Renal tubular dysfunction following treatment with anti-epileptic drugs

To evaluate renal side-effects of anti-epileptic medication in children, we performed a cross-sectional study of various aspects of renal function. We studied 59 patients from our outpatient clinic. They had been on anti-epileptic monotherapy for at least 3 months. None had a history of renal disease. Twenty-three healthy children of the same age group served as controls. After collecting 24-h urine samples, glomerular function was derived from creatinine clearance and from the excretion of albumin. Proximal tubular function was investigated by the urinary excretion of 1-microglobulin and of the tubular enzymes N-acetyl-ß-D-glucosaminidase, alamine-amino-peptidase and fructose-1,6-di-phosphatase. Distal tubular function was examined by the 24-h excretion of Tamm-Horsfall protein. On treatment with carbamazepine (n=27) and phenytoin (n=8), the excretion of 1-microglobulin was significantly increased, as compared with the healthy controls. On valproate (n=20), ethosuximide (n=9) and phenytoin (n=8), therapies significantly increased excretion of N-acetyl-ß-D-glucosaminidase. This must be interpreted as an indication of a functional disturbance of the proximal tubulus. The other parameters, indicating function of the glomerulus, loop of Henle and distal tubules did not differ from normal.Patients on anti-epileptic treatment with therapeutic drug levels may demonstrate minor signs of tubular dysfunction. These are probably insignificant from a clinical standpoint, but they should be considered in drug overdose.     

Renal Tubular Acidosis in a Case of Shwachman's Syndrome

ABSTRACT. We describe metabolic acidosis in a 15-month-old girl with clinical features of Shwachman's syndrome. Renal function tests indicated that the patient had type 1 renal tubular acidosis. Based on our findings and other reports of renal tubular dysfunction in patients with Shwachman's syndrome, we conclude that it is important to look for a possible renal tubular defect in this syndrome.     

Neurological outcome of methylmalonic acidaemia

OBJECTIVE: To assess the long term outcome of patients with methylmalonic acidaemia in a cross sectional study. PATIENTS: All 35 patients with methylmalonic acidaemia seen at Great Ormond Street Hospital for Children in London, UK between 1970 and 1996 were studied. They were divided into cobalamin responsive (n = 6) and non-responsive (n = 29), and early and late onset groups. RESULTS: There was a significant difference between cobalamin responsive and non-responsive groups in severity, survival, and incidence of neurological sequelae. Cobalamin responsive patients had mild disease, irrespective of age at presentation, their neurological complications were less severe, and they are all alive. The cobalamin non-responsive group comprised 19 early and nine late onset patients. The early onset patients had more severe disease at presentation and 14 have died; all late onset patients are alive. There was no significant difference in abnormal neurological signs, although early onset patients had a significantly reduced full scale intelligence quotient and poor cognitive outcome. In both groups, abnormal neurological signs continue to increase with age. CONCLUSIONS: Cobalamin responsive patients have a better long term outcome. The outcome in the non-responsive patients, particularly the early onset group, remains poor and alternative treatments should therefore be considered early in this group.     

Liver transplantation for methylmalonic acidaemia

The outcome for children with severe forms of methylmalonic acidaemia remains poor. Patients have recurrent episodes of metabolic decompensation; many have neurodevelopmental complications and the mortality is high. Long-term survivors develop chronic renal failure. Because of the poor prognosis, transplantation has been considered. In young patients with early onset disease, liver transplantation might prevent complications and, for those in end-stage renal failure, kidney transplantation could be combined with that of the liver. The results of liver transplantation in the early onset patients have generally been disappointing. In particular there appears to be a high risk of neurological complications. The optimal management of those in end-stage renal failure has not yet been determined although combined liver and kidney transplantation has been successful. Conclusion The role of transplantation in methylmalonic acidaemia has yet to be established and follow up of all patients who are considered for transplantation is essential.     

Chronic renal failure in methylmalonic acidaemia

The renal function of 12 patients with non vitamin B₁₂ responsive methylmalonic acidaemia has been investigated. Eight patients had reduced glomerular filtration rates, but the plasma creatinine concentration was only raised in those with values of less than 40ml/min per 1.73m² surface area. The reduction in glomerular filtration was a function of the age and the severity of the disease. Plasma urate concentrations were increased in four patients but this may be secondary to the renal disease rather than its cause.Abbreviations 51 Cr-EDTA 51-chromium ethylenediamine tetraacetic acid - GFR glomerular filtration rate - MMA methylmalonic acidaemia - SA surface area - TRP tubular reabsorption of phosphate - Ua/Uc urinary albumin/creatinine concentration ratio - Ul/Uc urinary lysozyme/creatinine concentration ratio     

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。     

Hashimoto thyroiditis,distal renal tubular acidosis,pernicious anaemia and encephalopathy: A rare combination of auto-immune disorders in a 12-year-old girl

A case of a 12-year-old girl with a multiple auto-immune disorder is reported. She showed Hashimoto thyroiditis which subsequently developed to hashitoxicosis and distal renal tubular acidosis at 5 years of age, pernicious anaemia at the age of 9 and severe encephalopathy at the age of 12. Laboratory studies revealed very high titres of anti-microsomal and anti-thyroglobulin antibodies and positive gastric parietal cell antibody. As to the encephalopathy, positive oligoclonal IgG bands and high values of IgG index and IgG synthesis ratio in CSF were observed with aggravation of her neurological symptoms. High-dose steroid therapy was effective toward the encephalopathy. Paediatricians should pay careful attention to patients with Hashimoto thyroiditis for association with other auto-immune disorders.     

Increased urinary excretion of tubular enzymes and proteins in children with epilepsy

Cross-sectional analysis of children undergoing treatment with anti-epileptic drugs has shown an increased urinary excretion of tubular enzymes and proteins. This has usually been interpreted as a consequence of subclinical renal-tubular damage or enzyme induction. We measured excretion of tubular enzymes and proteins in 29 children who suffered from epileptic seizures and in 27 control children. Investigations were undertaken at diagnosis before the start of treatment and 3-4 months later. At diagnosis we found a slightly, but statistically significant increased excretion of N-acetyl-beta-glucosaminidase and alpha1-microglobulin. There was no significant difference between patients with an idiopathic and symptomatic aetiology of seizures or between patients with different seizure types. At the second investigation, in children treated with carbamazepine or valproate, no further increase occurred. We conclude that the increased excretion of tubular enzymes and proteins in children with epilepsy is most probably not due to a side-effect of the anti-epileptic drugs, but to a physiological alteration associated with the epilepsy itself. While the cause is unknown, the influence of serotonin metabolism is discussed.     

An infant case of bilateral small kidneys with both proximal and distal tubular dysfunction

Abstract A male infant with bilateral small kidneys associated with both proximal and distal tubular dysfunction, who showed chronic renal failure soon after birth, is reported. He was also noted to have both proximal and distal type of renal tubular acidosis. The small kidneys were thought to be due to renal hypodysplasia associated with bilateral severe vesicoureteral reflux, by radiological findings. An alkalization therapy with chemo-prophylaxis seemed to be of benefit in slowing the progression of renal failure in this case.