NDT Advance Access originally published online on December 18, 2008
Nephrology Dialysis Transplantation 2009 24(5):1455-1464; doi:10.1093/ndt/gfn689
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Phenotype–genotype correlation in antenatal and neonatal variants of Bartter syndrome
1 Hôpitaux de Toulouse, Université Paul Sabathier, Département de Pédiatrie, Centre de Référence des Maladies Rénales Rares, Toulouse F31000 2 Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Hôpital Necker-Enfants Malades, Service de Néphrologie Pédiatrique, Centre de Référence des Maladies Rénales Héréditaires, Paris F75015 3 Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Hôpital Européen Georges Pompidou, Centre d’Investigations cliniques, Paris F75015 4 Assistance Publique-Hôpitaux de Paris, Université Paris 7, Hôpital Robert Debré, Service de Néphrologie Pédiatrique, Paris, F75019 5 Assistance Publique-Hôpitaux de Paris, Université Paris 6, Hôpital Trousseau, Service de Néphrologie Pédiatrique, Paris F75012 6 Hôpital Edouard Herriot, Université Claude Bernard-Lyon 1, Service de Néphrologie Pédiatrique, Centre de Référence des Maladies Rénales Héréditaires, Lyon F69000 7 Centre Hospitalier Universitaire de Montpellier, Service de Pédiatrie 1, Hôpital Arnaud de Villeneuve, Montpellier F34000 8 Centre Hospitalier Universitaire de Rouen, Département de Pédiatrie Médicale, Rouen F76000 9 Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Hôpital de la Timone, Service de Pédiatrie multidisciplinaire, Marseille F13000 10 Centre Hospitalier Universitaire de Nantes, Hôpital Mère et enfant, Service de Pédiatrie, Nantes F44000 11 Centre Hospitalier Régional Universitaire de Lille, Hôpital Jean de Flandre, Service de Néphrologie Pédiatrique, Lille F59000 12 Assistance Publique-Hôpitaux de Paris, Université Paris V, Hôpital Européen Georges Pompidou, Département de Génétique, Paris F75006, France
Correspondence and offprint requests to: Rosa Vargas-Poussou, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, F-75015 Paris, France. Tel: +33-1-56-09-30-31; Fax: +33-1-56-09-38-84; E-mail: rosa.vargas{at}egp.aphp.fr
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Abstract |
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Background. Ante/neonatal Bartter syndrome (BS) is a hereditary salt-losing tubulopathy due to mutations in genes encoding proteins involved in NaCl reabsorption in the thick ascending limb of Henle's loop. Our aim was to study the frequency, clinical characteristics and outcome of each genetic subtype.
Methods. Charts of 42 children with mutations in KCNJ1 (n = 19), SLC12A1 (n = 13) CLCNKB (n = 6) or BSND (n = 4) were retrospectively analysed. The median follow-up was 8.3 [0.4–18.0] years.
Results. We describe 24 new mutations: 10 in KCNJ1, 11 in SLC12A1 and 3 in CLCNKB. The onset of polyhydramnios, birth term, height and weight were similar for all groups; three patients had no history of polyhydramnios or premature birth and had CLCNKB mutations according to a less severe renal sodium wasting. Contrasting with these data, patients with CLCNKB had the lowest potassium (P = 0.006 versus KCNJ1 and P = 0.034 versus SLC12A1) and chloride plasma concentrations (P = 0.039 versus KCNJ1 and P = 0.024 versus SLC12A1) and the highest bicarbonataemia (P = 0.026 versus KCNJ1 and P = 0.014 versus SLC12A1). Deafness at diagnosis was constant in patients with BSND mutations; transient neonatal hyperkalaemia was present in two-thirds of the children with KCNJ1 mutations. Nephrocalcinosis was constant in KCNJ1 and SLC12A1 but not in BSND and CLCNKB patients. In most cases, water/electrolyte supplementation + indomethacin led to catch-up growth. Three patients developed chronic renal failure: one with KCNJ1 mutations during the second decade of age and two with CLCNKB and BSND mutations and without nephrocalcinosis during the first year of life.
Conclusions. We confirmed in a large cohort of ante/ neonatal BS that deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively. Chronic renal failure is a rare event, associated in this cohort with three genotypes and not always associated with nephrocalcinosis.
Keywords: Bartter syndrome; hyperkalaemia; hypokalaemia; nephrocalcinosis; phenotype/genotype
* These authors contributed equally to this work.
Received for publication: 7. 7.08
Accepted in revised form: 19.11.08