难治性Gitelman综合征1例及临床诊疗体会

目的  分析1例难治性Gitelman综合征的临床特点并总结其诊疗体会。方法  以1例Gitelman综合征患者为研究对象,完善相关检验检查以及肾脏病理、SLC12A3基因分析。结果  该患者青年起病,临床表现为反复心悸、发作性四肢抽搐、乏力,检查提示低钾、低镁、代谢性碱中毒,肾穿病理提示肾小球旁器增生,基因分析提示SLC12A3的复合杂合突变。治疗上予补钾、补镁及保钾,病情可缓解但易反复。结论  本例患者低钾更难纠正,极易复发,临床症状明显,值得长期关注。

     

Early diagnosis of Gitelman syndrome in a young child: A case report

BACKGROUNDGitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterized by renal wasting hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is usually caused by mutations in the gene SLC12A3, which encodes the thiazide-sensitive Na-Cl cotransporter. GS is not usually diagnosed until late childhood or adulthood.CASE SUMMARYHere, we report the case of a one-year-old girl who was brought to the emergency department due to persistent vomiting for two days. On admission to our hospital, generalized weakness was observed, and laboratory investigations revealed severe hypokalemia (1.9 mmol/L). However, persistent hypokalemia was observed during outpatient follow-up. Suspicion of the GS phenotype was assessed via the patient’s clinical presentation, family history, and biochemical analysis of blood and urine. Further genetic analysis was performed for her and her family by exon-wide sequencing analysis of the gene SLC12A3. The genetic diagnosis of GS was established in the Taiwanese family with three affected individuals, two of whom were children (7 years/17 years) without obvious symptoms, with the youngest being only one year old (patient in our case).CONCLUSIONWe successfully demonstrated the early diagnosis of GS using family genetic analysis. Any instances of hypokalemia should not be neglected, as early detection of GS with suitable treatment can prevent patients from potentially life-threatening complications.     

成人Bartter综合征2例报道并文献复习

目的 分析成人Bamer综合征的临床特点。方法 回顾性分析2例本病。结果 2例均为青年女性，均有不同程度的多饮、多尿、肌无力和抽搐；实验室检查均表现为低血钾、代谢性碱中毒，血肾素活性、血管紧张素Ⅱ及醛固酮明显升高，而血压正常；补钾、补镁、安体舒通等治疗后症状缓解，血钾水平升高。结论 成人出现双下肢乏力，低血钾碱中毒，而血压正常时需考虑本病，本病行立-卧位肾素-血管紧张素-醛固酮测定可基本诊断，必要时行肾穿刺活检；治疗以补钾为主，辅助治疗包括补镁、前列腺素合成酶抑制剂、醛固酮拮抗剂等。     

Hypercalcemia Reduces Renal Medullary Content of Organic Osmolytes

Hypercalcemia is often associated with a urinary concentration defect. During antidiuresis, organic osmolytes [sorbitol, myo-inositol, taurine, and glycerophosphorylcholine (GPC)] accumulate in the renal inner medulla and are essential for urinary concentration. To clarify the relationship between organic osmolytes and urinary concentration defect in hypercalcemia, examination was made of the effects of hypercalcemia on renal medullary osmolytes content. Rats were put in a state of hypercalcemia by a calcium-rich diet supplemented with CaCO₃ (2.5%/wt) anddaily s.c. injection of I,25(OH)₂ VitD₃ (1.6 μg/kg). They were killed on days 7 and 14. Hypercalcemia induced a urinary concentration defect. Myo-inositol, sorbitol, and GPC contents in the renal medulla were significantly reduced. Aldose reductase activity decreased significantly. Hypercalcemia would thus appear to directly affect renal medullary content of organic osmolytes, thereby modifying renal concentration ability.     

Prise en charge de la grossesse chez des patientes atteintes de syndrome de Gitelman : série de 12 cas

IntroductionGitelman syndrome is a rare hereditary renal tubulopathy, responsable of hypokalemia and hypomagnesaemia-related ionic disorders, which management is poorly codified during pregnancy. We report 12 cases of pregnancies with Gitelman syndrome and we compare our data with those of literature.Material and methodsIt is a report of 12 pregnancies in 5 patients with Gitelman syndrome between 2002 and 2016. Follow up and outcome of pregnancy, delivery modalities and maternal-fetal prognosis have been collected.ResultsIn our serie, maximum kaliemie observed was 3.4 mmol/L, with an average potassium, over all pregnancies of 2.3 mmol/L. Oral potassium and magnesium supplementation at the end of pregnancy were 8900 mg/day and 460 mg/day, respectively. There were no serious maternal complications. Two pregnancies were complicated by intrauterine growth retardation in a context of preeclampsia. There is a large disparity in the methods of anesthetic management of these patients. Materno-fetal prognosis at 1 month post-partum is good.ConclusionGitelman syndrome is a rare pathology where there is a lack of homogeneity in management of pregnancy. Monitoring of monthly ionogram is necessary. The goal is to obtain stable, non-symptomatic kaliemias, which will never be standardized even in increasing treatment. The most important is to inform and detect situations at risk of decompensation, including vomiting or the use of certain anesthetics. In agreement with literature data, monitoring of fetal growth and the amount of amniotic fluid in the third trimester is still warranted. These pregnancies require the development of a common care in multidisciplinary consultation meeting.     

Gitelman’s syndrome and pregnancy: new potential pathophysiological influencing factors,therapeutic approach and materno-fetal outcome

In the last twenty years the knowledge of biochemical, hormonal and molecular abnormalities of Gitelman’s syndrome, the most common phenotype of inherited hypokalemic salt losing renal tubular disorders, is increased in the medical community. In parallel with the increasing number of adult population affected by the syndrome and the remarkable improvement of its management, pregnancy have become an important issue for patients affected and their physicians. There are, however, few reports of pregnancies in Gitelman’s patients. We review here the cases of pregnancies in Gitelman’s patients reported in literature and report three more cases from our cohort of Gitelman’s patients, giving particular attention to the materno-fetal outcome and therapeutic approach. The possible influences on pregnancy of Gitelman’s patient of other main hemodynamic, hormonal and molecular features of Gitelman’s syndrome such as cardiovascular hyporesponsiveness, abnormal vascular tone regulation, upregulation of nitric oxide and Angiotensin 1–7 systems with their possible influence on the reported alteration of cardiac rhythm and function, are also considered.