Bartter and Gitelman syndromes:Spectrum of clinical manifestations caused by different mutations

Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases,recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition.Although they share some characteristic metabolic abnormalities such as hypokalemia,metabolic alkalosis,hyperplasia of the juxtaglomerular apparatus with hyperreninemia,hyperaldosteronism,the clinical and laboratory manifestations may not always allow distinction between them.Diuretics tests,measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change(< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS,except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists.The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children.Clinical symptoms and biochemical markers of GS and classic form of BS(type III) may overlap and thus genetic analysis may specify the real cause of symptoms.However,although genetic analysis is available,its use remains limited because of limited availability,large gene dimensions,lack of hot-spot mutations,heavy workup time and costs involved.Furthermore,considerable overlap exists between the different genotypes and phenotypes.Although BS and GS usually have distinct presentations and are associated with specific gene mutations,there remains considerable overlap between their phenotypes and genotypes.Thus,they are better described as a spectrum of clinical manifestations caused by different gene mutations.

Significance of platelet count in children admitted with bronchiolitis

AIM To determine the true prevalence of thrombocytosis in children less than 2 years of age with bronchiolitis,its association with risk factors,disease severity and thromboembolic complications.METHODS A retrospective observational medical chart review of 305 infants aged two years or less hospitalized for bronchiolitis.Clinical outcomes included disease severity,duration of hospital stay,admission to pediatric intensive care unit,or death.They also included complications of thrombocytosis,including thromboembolic complications such as cerebrovascular accident,acute coronary syndrome,deep venous thrombosis,pulmonary embolus,mesenteric thrombosis and arterial thrombosis and also hemorrhagic complications such as bleeding(spontaneous hemorrhage in the skin,mucous membranes,gastrointestinal,respiratory,or genitourinary tracts).RESULTS The median age was 4.7 mo and 179 were males(59%).Respiratory syncytial virus was isolated in 268(84%),adenovirus in 23(7%) and influenza virus A or B in 13(4%).Thrombocytosis(platelet count > 500 × 109/L) occurred in 88(29%;95%CI:24%-34%),more commonly in younger infants with the platelet count declining with age.There was no significant association with the duration of illness,temperature on admission,white blood cell count,serum C-reactive protein concentration,length of hospital stay or admission to the intensive care unit.No death,thrombotic or hemorrhagic events occurred.CONCLUSION Thrombocytosis is common in children under two years of age admitted with bronchiolitis.It is not associated with disease severity or thromboembolic complications.