Limited phenotypic variability has been reported in patients with Bartter syndrome type I, with mutations in the Na-K-2Cl cotransporter gene (BSC). The diagnosis of this hereditary renal tubular disorder is usually made in the antenatal-neonatal period, due to the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis. Among nine children with hypercalciuria and nephrocalcinosis, we identified new mutations consistent with a loss of function of the mutant allele of the BSC gene in five. Three of the five cases with BSC gene mutations were unusual due to the absence of hypokalemia and metabolic alkalosis in the first years of life. The diagnosis of incomplete distal renal tubular acidosis was considered before molecular evaluation. Three additional patients with hypokalemia and hypercalciuria, but without nephrocalcinosis in the first two and with metabolic acidosis instead of alkalosis in the third, were studied. Two demonstrated the same missense mutation A555T in the BSC gene as one patient of the previous group, suggesting a single common ancestor. The third patient presented with severe hypernatremia and hyperchloremia for about 2 months, and a diagnosis of nephrogenic diabetes insipidus was hypothesized until the diagnosis of Bartter syndrome type I was established by molecular evaluation. We conclude that in some patients with Bartter syndrome type I, hypokalemia and/or metabolic alkalosis may be absent in the first years of life and persistent metabolic acidosis or hypernatremia and hyperchloremia may also be present. Molecular evaluation can definitely establish the diagnosis of atypical cases of this complex hereditary tubular disorder, which, in our experience, may exhibit phenotypic variability.

In a series of 325 HBV chronically infected children observed over an 18-year period, three developed HCC. These three children were born in southern Italy, a region characterized by a high endemic HBV infection rate; each had been infected perinatally, developed an acute hepatitis, and became a chronic carrier. Two of the three with cirrhosis were HBsAg positive at the time their HCC was detected. The remaining case had seroconverted to HBsAb but HBV-DNA integration could be demonstrated in the absence of cirrhosis; moreover HBV antigens were not expressed in the tissue of this case. The interval between HBV infection and HCC appearance in these three cases ranged from six to 11 years. A similarity between these three Italian cases and the majority of HCC arising in chronically infected children in the Far East is noted.

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