ABSTRACT
BACKGROUND: Little information is available on a long-term follow-up in Bartter syndrome type I and II. METHODS: Clinical presentation, treatment and long-term follow-up (5.0-21, median 11 years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. RESULTS: Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90 mL/min/1.73 m(2) in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. CONCLUSIONS: Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Gallstones might represent a new complication of antenatal Bartter syndrome.
Subject(s)
Bartter Syndrome/genetics , Mutation/genetics , Potassium Channels, Inwardly Rectifying/genetics , Sodium-Potassium-Chloride Symporters/genetics , Bartter Syndrome/classification , Bartter Syndrome/drug therapy , Body Height , Body Weight , Child, Preschool , Female , Follow-Up Studies , Glomerular Filtration Rate , Heterozygote , Homozygote , Humans , Infant , Infant, Newborn , Male , Prognosis , Solute Carrier Family 12, Member 1 , Time FactorsABSTRACT
Both human linkage studies and MC3R knockout mouse models suggest that the MC3R may play an important role in energy homeostasis. Here we show that among 355 overweight and nonoverweight children, 8.2% were double homozygous for a pair of missense MC3R sequence variants (Thr6Lys and Val81Ile). Such children were significantly heavier (BMI and BMI SD score: P < 0.0001), had more body fat (body fat mass and percentage fat mass: P < 0.001), and had greater plasma leptin (P < 0.0001) and insulin concentrations (P < 0.001) and greater insulin resistance (P < 0.008) than wild-type or heterozygous children. Both sequence variants were more common in African-American than Caucasian children. In vitro expression studies found the double mutant MC3R was partially inactive, with significantly fewer receptor binding sites, decreased signal transduction, and less protein expression. We conclude that diminished MC3R expression in this double MC3R variant may be a predisposing factor for excessive body weight gain in children.
