Clinical and diagnostic features of Bartter and Gitelman syndromes

Walsh, Patrick R.; Tse, Yincent; Ashton, Emma; Iancu, Daniela; Jenkins, Lucy; Bienias, Marc; Kleta, Robert; Hoff, William van’t; Böckenhauer, Detlef

doi:10.1093/ckj/sfx118

Cited by 61 publications

(100 citation statements)

References 32 publications

(31 reference statements)

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“…Chronic hypomagnesaemia is thought to cause the development of chondrocalcinosis that can be a complication in adult patients with GS. There can be some degree of polyuria and polydipsia, but this is generally less profound compared to patients with BS and, at least in childhood, urinary concentrating ability appears intact [21,28].…”

Section: Gitelman Syndromementioning

confidence: 99%

“…Patients present with polyuria (which, depending on the subtype, can manifest antenatally with polyhydramnios and preterm birth), hypokalaemic, hypochloraemic metabolic alkalosis and normal blood pressure in the context of elevated renin and aldosterone levels. On a genetic basis, 5 different subtypes are currently distinguished (Table 1) [3,4,21].…”

Section: Bartter Syndromesmentioning

confidence: 99%

“…When using this classification, BS is generally considered a disorder of TAL, whereas GS is a disorder of DCT function. Yet, confusingly, some subtypes of BS also affect the DCT and, in fact, BS3 can be clinically indistinguishable from GS [3,4,21,28,32,33]. For this reason, a classification has been proposed, separating the various types into disorders of the TAL, the DCT, or of both segments [13].…”

Section: Problems With the Current Classificationmentioning

confidence: 99%

“…The genetic causes are usually mutations in SLC12A1 (NKCC2) or KCNJ1 (KCNJ1). In contrast, disorders of the DCT are characterized by hypo-or normocalciuria, hypomagnesaemia and typically manifest later in childhood or adolescence [3,4,21,28]. The pharmacologic equivalent here is thiazide diuretics and the genetic causes are usually mutations in CLCNKB or SLC12A3 (NCC).…”

Section: Problems With the Current Classificationmentioning

confidence: 99%

“…Although most patients with BS and GS nowadays have a genetic confirmation of their diagnosis, there is still a significant group of patients with a BS phenotype in whom no disease-causing mutation could be detected. New techniques, including whole-exome/genome sequencing, could identify other genes that can cause BS and GS and increase our knowledge of the exact mechanisms of tubular solute handling [3,4,21]. For instance, the recent discovery that vesicle-associated membrane protein 3 (VAMP3) is needed for accurate intracellular trafficking of NKCC2 to the luminal membrane, and that Vamp3 -/mice exhibit a BS phenotype, would make this an interesting candidate gene [51].…”

Section: Future Considerationsmentioning

confidence: 99%

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Bartter and Gitelman syndromes: Questions of class

2019

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Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications. These problems mostly relate to uncertainties over the role of the basolateral chloride exit channel CLCNKB, expressed in both TAL and DCT and to what degree the closely related paralogue CLCNKA can compensate for the loss of CLCNKB function. Here, we review what is known about the physiology of the transport proteins involved in these disorders. We also review the various proposed classifications and explain why a gene-based classification constitutes a pragmatic solution.

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Section: Gitelman Syndromementioning

confidence: 99%

Section: Bartter Syndromesmentioning

confidence: 99%

Section: Problems With the Current Classificationmentioning

confidence: 99%

Section: Problems With the Current Classificationmentioning

confidence: 99%

Section: Future Considerationsmentioning

confidence: 99%

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Bartter and Gitelman syndromes: Questions of class

2019

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A novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate

Yaprak,

Kara,

Calisici

et al. 2023

Birth Defects Research

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BackgroundBartter syndrome (BS) is a rare congenital salt‐losing renal tubular transport disorder, characterized by salt wasting, polyuria, biochemical abnormalities, and acid–base homeostasis imbalance. The syndrome has five different genetic forms, and novel mutations of CLCNKB gene lead to type 3 BS also known as classic BS. In this case, we report clinical and molecular findings from a newborn baby with BS.CaseA 10‐day‐old male infant born at 37 weeks of gestation by cesarean section following a pregnancy complicated with polyhydramnios, and fetal distress to a 30‐year‐old gravida 3, para 3 mother, with a 2500 g birth weight was brought to the pediatric emergency department due to weight loss and jaundice. The neonate was referred to the neonatal intensive care unit (NICU) with a preliminary diagnosis of hyponatremic dehydration (Na: 122 mmol/L, 10% dehydration) and hypokalemic hypochloremic metabolic alkalosis (K: 2.13 mmol/L, Cl: 63 mmol/L, pH: 7.62, pCO2: 39 mmHg, HCO3: 40.8 mmol/L, BE: 16.9 mmol/L), and hypocalcemia (ionized Ca: 0.72 mmol/L). On arrival to the NICU, symptomatic focal seizures, and polyuria complicated his course. Spot urine biochemistry revealed a renal salt wasting and hypercalciuria: Creatine 11.4 mg/dL Na: 51 mmol/L (54–150), K: 26 mmol/L (20–80), Cl: 164 mmol/L, fractional excretion of sodium (FENa): 3% (0.9–1.6), fractional excretion of chloride (FECl): 17% (<0.5%) and Ca/Cr: 0.33 (<0.2). Biochemical abnormalities disappeared through intravenous fluid and electrolyte therapy, but he could not achieve adequate weight gain, and polyuric urine output (6.5 cc/kg/h), and metabolic alkalosis continued as the enteral feedings advance. Patient's serum renin: 184 pg/mL (5–27 pg/mL) and aldosterone: 1670 pg/mL (1–180 ng/dL) were elevated. Polyuria, renal salt wasting, electrolyte and acid–base disturbances, and hyperreninemic hyperaldosteronism established the diagnosis as Bartter syndrome. An oral indomethacin (1 mg/kg/day) treatment, on the 8th day. ensured the weight gain, and normalized daily urine output. He achieved the goal of birth weight on the 30th day and he was 3520 g weight at discharge on day 42. The genetic tests of the patient as KCNJ1 SLC12A1 gene sequence analysis revealed a novel homozygous mutation in the 14th exon of the CLCNKB gene, the c.1334_1338del CTTTT (p. Ser445fs*4) variant was identified.DiscussionThe diagnosis of BS should be considered in the presence of a medical history of severe polyhydramnios of fetal origin. Postnatally, polyuria, signs of dehydration, renal salt wasting, and hypokalemic‐metabolic alkalosis should prompt the clinician to request genetic testing for BS in the neonatal period. This case is presented to emphasize that early diagnosis of BS should be considered in newborns presenting with electrolyte abnormalities and metabolic alkalosis accompanying dehydration and favorable growth results can be achieved by starting indomethacin treatment in the early neonatal period. The clinical exome sequencing illustrated a novel missense variant in the CLCNKB gene leading to the molecular diagnosis of BS type 3.

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