Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies

Hypokalemic salt-losing tubulopathies (Bartter-like syndromes) comprise a set of clinically and genetically distinct inherited renal disorders. Mutations in four renal membrane proteins involved in electrolyte reabsorption have been identified in these disorders: the furosemide-sensitive sodium-pota...

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Bibliographic Details
Published in:	The American journal of medicine Vol. 112; no. 3; p. 183
Main Authors:	Peters, Melanie, Jeck, Nikola, Reinalter, Stephan, Leonhardt, Andreas, Tönshoff, Burkhard, Klaus G, G ünter, Konrad, Martin, Seyberth, Hannsjörg W
Format:	Journal Article
Language:	English
Published:	United States 15-02-2002
Subjects:	Algorithms Carrier Proteins - genetics Gestational Age Humans Hypokalemia - drug therapy Hypokalemia - genetics Hypokalemia - physiopathology Infant, Newborn Linear Models Mutation Phenotype Potassium - therapeutic use Potassium Channels - genetics Potassium Channels, Inwardly Rectifying Receptors, Drug Renal Tubular Transport, Inborn Errors - genetics Renal Tubular Transport, Inborn Errors - metabolism Sodium Chloride Symporters Sodium-Potassium-Chloride Symporters - genetics Solute Carrier Family 12, Member 1 Solute Carrier Family 12, Member 3 Symporters
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Summary:	Hypokalemic salt-losing tubulopathies (Bartter-like syndromes) comprise a set of clinically and genetically distinct inherited renal disorders. Mutations in four renal membrane proteins involved in electrolyte reabsorption have been identified in these disorders: the furosemide-sensitive sodium-potassium-chloride cotransporter NKCC2, the potassium channel ROMK, the chloride channel ClC-Kb, and the thiazide-sensitive sodium-chloride cotransporter NCCT. The aim of this study was to characterize the clinical features associated with each mutation in a large cohort of genetically defined patients. The phenotypic characteristics of 65 patients with molecular defects in NKCC2, ROMK, ClC-Kb, or NCCT were collected retrospectively. ROMK and NKCC2 patients presented with polyhydramnios, nephrocalcinosis, and hypo- or isosthenuria. Hypokalemia was less severe in the ROMK patients compared with the NKCC2 patients. In contrast, NCCT patients had hypocalciuria, hypomagnesemia, and marked hypokalemia. While this dissociation of renal calcium and magnesium handling was also observed in some ClC-Kb patients, a few ClC-Kb patients presented with hypercalciuria and hypo- or isosthenuria. ROMK, NKCC2, and NCCT mutations usually have uniform clinical presentations, whereas mutations in ClC-Kb occasionally lead to phenotypic overlaps with the NCCT or, less commonly, with the ROMK/NKCC2 cohort. Based on these results, we propose an algorithm for the molecular diagnosis of hypokalemic salt-losing tubulopathies.
ISSN:	0002-9343
DOI:	10.1016/S0002-9343(01)01086-5