부산대학교 도서관

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 Henleʼs 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.