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Background It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. Methods This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n = 93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n = 34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. Results Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. Conclusions The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.

Decreased Trabecular Bone Mineral Density in Children with Idiopathic Short Stature. Normalization of Bone Density and Increased Bone Turnover after One Year of Growth Hormone Treatment

We have recently demonstrated that children and adolescents with IDDM present with decreased lumbar spine BMD as early as 5 years after diagnosis. The purpose of this study was to evaluate the bone mineral status in a group of newly diagnosed children (9.0±1.9 months after diagnosis). We studied 10 children (5 males and 5 females) with a mean chronological age of 9.9±1.7 years and a mean glycosilated hemoglobin of 8.6±0.8%. Lumbar spine and femoral neck BMD were measured by dual X-Ray absorptiometry, while bone turnover was asssessed by the determination of the serum concentrations of the carboxy-terminal propeptide of type 1 procollagen (PICP) and the carboxy-terminal cross-linked telopeptide of type 1 collagen (ICTP). Results were compared to those of age, height, weight and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in our patients when compared to controls (Z-scores were -1.5±0.3, with eight out of ten patients showing values >1SD below the mean). No significant differences were noted in femoral neck BMD and total bone mineral content between groups. Serum PICP levels were decreased when compared to controls(233.6±39.3 vs 375.9±50.7 ug/L; p< 0.002), while serum ICTP concentrations, although increased, were not significantly different(9.3±1.3 vs 5.7±1.5 ug/L). However, PICP and ICTP did not correlate with the lumbar spine Z-score. In summary, early after diagnosis IDDM children present with decreased lumbar spine BMD and decreased bone formation markers.

We have previously shown that prepubertal girls with TS on growth hormone have normal BMD. The present study reevaluates the BMD, as assessed by dual X ray absorptiometry, of the original 8 girls; they are now 18.25±1.06 years of age, in Tanner stage V of puberty and have reached a final height of 149.5±6.2 cm. They have been off growth hormone for 3.8±0.9 years and on conjugated estrogens (0.625 mg daily) continuously for 4.1±1.0 years. The results were compared to our own reference data of age and gender related controls and to literature reference data which allow for comparison with girls of similar weight and pubertal status. Lumbar spine BMD was significantly reduced in our patients when compared to age and gender controls (mean Z score of -3.26±0.43, with 7 out of 8 patients with Z-scores >2 SD below the mean). When the lumbar spine BMD was compared to controls of similar weight and pubertal status it was still reduced, but to a lesser degree (mean Z-score of -1.06±0.53 with only 2 patients showing Z-scores >2 SD below the mean). When we compared the femoral neck and lumbar spine BMD of our subjects, as adults on estrogen replacement, to that obtained 6 years ago while they were prepubertal and on growth hormone, no significant change was found despite a mean increase in their height during this period of 18.4±3.5 cm (BMD of 0.758±0.04 and 0.779±0.05 g/cm2 in femoral neck and lumbar spine, respectively, while prepubertal and on growth hormone vs 0.754±0.03 and 0.816±0.03 g/cm2 as adults on estrogen replacement). The serum concentrations of the carboxyterminal propeptide of type 1 procollagen are decreased (p< 0.05), while the serum levels of the carboxyterminal cross-linked telopeptide of type 1 collagen are increased in our patients when compared to controls (p

We evaluated 91 newly diagnosed IDDM children mean age 7.8 ± 4.5 yrs; 56.7% had had an upper respiratory infection prior to diagnosis and 12.7% had had either mumps or varicella. Peak incidence of disease was found in February and March and August to October. Eighty seven percent had HLA-DR3 and/or DR4 vs 37% of the Venezuelan general population; 81.6% were HLA-DQW2 and/or HLA-DQW8. Studies of oligonucieotid hybridization showed the presence of arginine in position 52 of the DQ alpha chain and absence of aspartic acid in position 57 of the DQ beta chain, with an increased prevalence of DR2 and especially with DQB1 0602 which has been associated with protection. We found 55.9% to have positive islet cell antibodies (ICA) with 4 of these having a positive complement fixation test. Three patients (7.9%) were found to have positive insulin autoantibodies. No positive serotypes for enterovirus (Coxsackie-B) were found in our patients, but we detected 11 cases with elevated titers for cytomegalovirus antibodies. Positive antibodies for measles, mumps, herpes and varicella were found in some children. This study contributes to a better understanding of the epidemiology and immunogenetics of insulin dependent diabetes mellitus in Latin-American children.