Cocaine- and amphetamine-regulated transcript (CART) inhibits feeding and induces the expression of c-Fos in hypothalamic areas implicated in appetite regulation. Furthermore, the CART peptide is found in neurons regulating sympathetic outflow, which in turn play an integral role in regulating body temperature and energy expenditure. The CART gene was screened by single-strand conformation polymorphism and automatic sequencing in 130 (72 girls) unrelated obese Italian children and adolescents. Their Z-scores (mean +/- SD) of relative to BMI percentiles was 3.9 +/- 1.8, and the average age at obesity onset was 4.7 +/- 2.6 years. Two previously described silent polymorphisms were found in the 3' untranslated region: an adenine deletion at position 1457 in 9 patients (allele frequency 0.035) and an A/G substitution at position 1475 in 11 patients (allele frequency 0.042). We found no difference between the obese patients heterozygous for one of these polymorphisms and those patients homozygous for the wild allele with respect to their age of obesity onset, BMI Z-scores, and leptin levels. A missense mutation of G729C resulting in the substitution of Leu with Phe at codon 34, within the NH2-terminal CART region, has been detected in the heterozygous state in a 10-year-old obese boy who has been obese since the age of 2 years. The patient belongs to a large family of obese subjects. The mutation cosegregated with the severe obesity phenotype over three generations and was not found in the control population. Resting metabolic rates were lower than expected in the propositus (-14%) and his mother (-16%), who carried the mutation. Leucine at codon 34, conserved in this position in the human and in the rat sequences, immediately precedes a couple of lysine residues that may well represent a dibasic processing site. The Leu34Phe mutation might alter the susceptibility to proteolysis of this potential processing site, likely altering the CART effect on thermogenesis and energy expenditure.

Idiopathic hypercalciuria (IHC) has been reported mainly in children with hematuria in the 1980s and early 1990s, when renal sonography was just becoming routine. The presence of microcalculi, i.e., of hyperechogenic spots < 3 mm in diameter in renal calyces, was not taken into account in those studies. We attempted to outline clinical presentation and natural course of IHC not only in children with hematuria, but also in those with dysuria and/or recurrent abdominal/flank pain and a family history of nephrolithiasis, taking into account the finding of microcalculi. We analyzed retrospectively the data at diagnosis from 74 consecutive children aged 2.4-18 years (mean 8.6) with IHC (calciuria 4.1-15.1 mg kg-1 24 h-1, mean 6.1) and the outcome of 30 of them who were followed > or = 1 years (mean 3.2) with no specific therapy. At diagnosis, 38 patients (51%) had no hematuria, 42 (57%) had microcalculi and four (5%) had calculi. Of the patients with normal urinalysis, 71% had microcalculi or stones. The subjects with microcalculi and those with stones were significantly older than those without microcalculi and stones (P = 0.004 and 0.007). A normal urinalysis at our evaluation and a history of abdominal/flank pain were significantly more frequent in patients with microcalculi than in those without (P = 0.02 and 0.0001, respectively). During the follow-up, four of 30 patients formed stones 1-3 years after first diagnosis of IHC. More than half of children with IHC have microcalculi. The risk of formation of microcalculi or stones increases with age. The lack of hematuria does not exclude the presence of microcalculi or calculi. Hypercalciuria has to be suspected in children with dysuria and/or recurrent abdominal flank pain and a family history of nephrolithiasis, even when they have no hematuria.

Zinc and copper status was examined in 19 healthy and 43 atopic children (22 asthmatics and 21 eczematous) 2-14 years old. Dietary intakes for energy, protein, zinc and copper and some nutritional indices (height, weight, serum protein, albumin, ceruloplasmin) were similar in the allergic and in the control group. The proton-induced X-ray fluorescence technique was used to assess zinc and copper concentrations in serum and hair. No difference was detected in serum zinc concentration between allergic and healthy children. In contrast, mean hair zinc level was lower (p less than 0.05) in allergic than in healthy children (99 +/- 6 vs. 147 +/- 9 micrograms/g). Mean serum copper content was higher in asthmatic than in control children while mean hair copper was higher (p less than 0.05) in asthmatic and eczematous children than in the control group. These findings suggest a different zinc and copper nutritional status between allergic and healthy subjects. Allergic children, in particular, seem to be a risk of zinc deficiency.

Mutations in codons 7 and 9 of the signal peptide may alter the translocation of the pre-proopiomelanocortin into the endoplasmic reticulum and, therefore, can be implicated in obesity. Although further studies are required, the polymorphism between position 6997 and 6998 may represent one of the genetic variations that explain the linkage between obesity and POMC. International Journal of Obesity (2001) 25, 61-67

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