Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome

被引：115

作者：

Brochard, Karine ^{[2
]}

Boyer, Olivia ^{[3
]}

Blanchard, Anne ^{[1
]}

Loirat, Chantal ^{[4
]}

Niaudet, Patrick ^{[3
]}

Macher, Marie-Alice ^{[4
]}

Deschenes, Georges ^{[4
]}

Bensman, Albert ^{[5
]}

Decramer, Stephane ^{[2
]}

Cochat, Pierre ^{[6
]}

Morin, Denis ^{[7
]}

Broux, Francoise ^{[8
]}

Caillez, Mathilde ^{[9
]}

Guyot, Claude ^{[10
]}

Novo, Robert ^{[11
]}

Jeunemaitre, Xavier ^{[12
]}

Vargas-Poussou, Rosa ^{[1
,12
]}

机构：

[1] Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, Ctr Invest Clin, F-75015 Paris, France

[2] Univ Toulouse 3, Hop Toulouse, Dept Pediat, Ctr Reference Malad Renales Rares, F-31000 Toulouse, France

[3] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Serv Nephrol Pediat,Ctr Reference Malad Renales H, F-75015 Paris, France

[4] Univ Paris 07, Hop Robert Debre, AP HP, Serv Nephrol Pediat, F-75019 Paris, France

[5] Univ Paris 06, Hop Trousseau, AP HP, Serv Nephrol Pediat, F-75012 Paris, France

[6] Univ Lyon 1, Hop Edouard Herriot, Serv Nephrol Pediat, Ctr Reference Malad Renales Hereditaires, F-69000 Lyon, France

[7] CHU Montpellier, Hop Arnaud Villeneuve, Serv Pediat 1, F-34000 Montpellier, France

[8] Ctr Hosp Univ Rouen, Dept Pediat Med, F-76000 Rouen, France

[9] Univ Aix Marseille 2, Hop Timone, Assistance Publ Hop Marseille, Serv Pediat Multidisciplinaire, F-13000 Marseille, France

[10] CHU Nantes, Hop Mere & Enfant, Serv Pediat, F-44000 Nantes, France

[11] Ctr Hosp Reg Univ Lille, Hop Jean Flandre, Serv Nephrol Pediat, F-59000 Lille, France

[12] Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, Dept Genet, F-75006 Paris, France

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2009年 / 24卷 / 05期

关键词：

Bartter syndrome; hyperkalaemia; hypokalaemia; nephrocalcinosis; phenotype; genotype; HYPERPROSTAGLANDIN-E SYNDROME; CHLORIDE CHANNEL GENE; NA-K-2CL COTRANSPORTER NKCC2; GLOMERULAR-FILTRATION-RATE; SALT-LOSING TUBULOPATHIES; SENSORINEURAL DEAFNESS; HYPOKALEMIC ALKALOSIS; MOUSE KIDNEY; RENAL-DISEASE; BETA-SUBUNIT;

D O I：

10.1093/ndt/gfn689

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

1001 ; 1002 ; 100602 ;

摘要：

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.

引用

页码：1455 / 1464

页数：10

共 47 条

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