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The salt-losing tubulopathies are rare diseases that can present in infancy or later in childhood with renal salt wasting, hypokalemic hypochloremic metabolic alkalosis, and normal blood pressure despite hyperreninemia and hyperaldosteronism; Treatment varies by type but may include ample fluid delivery, electrolyte replacement, nutritional support, prostaglandin inhibition, and disruption of renin-angiotensin-aldosterone axis.
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Antenatal Bartter/hyperprostaglandin E syndrome presents with fetal
Bartter Syndrome and Gitelman Syndrome
Section snippets
Key points
History
In 1962, Dr Frederic Bartter described 2 African American patients with severe hypokalemic alkalosis, normotensive hyperaldosteronism, and hyperplasia and hypertrophy of the juxtaglomerular apparatus.3 Several years later, Gitelman and colleagues4 described a similar but distinct syndrome in 3 patients who had these findings and impaired renal conservation of magnesium. As more cases of suspected BS and GS were described, it was noted that the clinical symptoms correlated closely with those of
Clinical presentation
Although variants of BS and GS are genotypically distinct, there is considerable overlap in clinical presentation. Clinically, these tubulopathies are often categorized into several major groups: antenatal BS (ABS) or hyperprostaglandin E syndrome (HPES), classic BS (CBS), and GS. Other related syndromes (Box 1) have overlapping clinical features and so are included in this discussion. All share the characteristics of renal salt wasting, hypokalemic hypochloremic metabolic alkalosis, and low or
Variants of Bartter and Gitelman syndromes and related conditions
Classification schemes of BS, GS, and related syndromes are in evolution. Historically, patients were categorized by phenotypic characteristics (ABS vs CBS based on age and severity of presentation); however, emerging data about genetic variants and unique and distinct mechanisms of salt-wasting present a new gene-based framework for classification. Moreover, there is variation in clinical presentation even when the same gene is affected (eg, BS type III can present antenatally or later in
Diagnosis
BS and GS comprise a spectrum with overlapping characteristics that can present with varying levels of severity, making diagnosis difficult. A careful history, physical examination, and laboratory evaluation should be undertaken (Box 2), with genetic testing to be considered to confirm the fundamental defect and diagnosis. Age at diagnosis can help distinguish between an ABS variant and CBS or GS. In a premature neonate with polyuria and poor weight gain, it may be tempting to suspect NDI;
Management
Acute management in dehydrated patients involves correcting water losses and repleting electrolytes. Chronically, patients require electrolyte supplementation and inhibition of prostaglandin production and/or the RAAS,12 although comprehensive clinical studies examining efficacy and outcome are lacking. Patients with BS and GS are typically prescribed oral salt replacement therapy, although normalizing serum electrolytes with an ongoing tubular leak is challenging, optimal frequency of dosing
End-stage renal disease transplant
BS and GS rarely advance to end-stage renal disease (ESRD) and renal failure. In those who have progressed as a result of chronic nephropathy or medication side effects, renal transplant has proven successful.49, 50 Preemptive bilateral nephrectomy with subsequent transplantation has been performed in 2 patients with severe, debilitating ABS before the onset of ESRD in an effort to cure the underlying disease and improve quality of life,51 though this is not standard practice.
Summary
BS and GS patients demonstrate how dramatic the impact of impaired renal salt transport can be. Depending on the setting, certain red flags should prompt the clinician to consider these conditions, including polyhydramnios in the neonatal intensive care unit, chronic weakness exacerbated by gastrointestinal losses in the urgent setting, and poor growth identified at the well-child visit. Assessment of the basic metabolic panel and serum magnesium can be informative and can guide next steps.
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Disclosures: No relevant disclosures.