To recognize patients with 21- and/or 11betaOHD, we recommend evaluation of 17OHP or 21DF and S. Also, 21DF may be useful to follow up pubertal patients with 21OHD. Because 1% of patients with alleged 21OHD may have 11betaOHD, its frequency seems underestimated, as per our experience in a Brazilian population.

Turner syndrome (TS) is characterized by the presence of an X chromosome and total or partial loss of the second sex chromosome, short stature, hypergonadotrophic hypogonadism, and a variable dysmorphic picture. Delayed puberty and estrogen deficiency are some of the determinant factors of osteoporosis in TS, but the whether or not there is an intrinsic bone defect is still obscure. The aim of this study was to evaluate the correlation of the z score of bone mineral density (BMD) with age, weight, height, karyotype, associated diseases, bone age, and estrogen therapy in TS patients. We performed a transverse study with area BMD of L2-L4 with dual-energy X-ray absorptiometry (DEXA) in 58 patients with a cytogenetic diagnosis of TS, whose ages ranged from 5 to 29 years. It was observed that 86% of the patients presented with a BMD z score below -1 SD, and 46.5% with a value below -2.5 SD. There was a significant negative association of BMD with age and height, and a positive association with weight and bone mass index (BMI) z scores. A higher BMD was observed in patients with spontaneous puberty and in those with more than 2 years of hormone replacement. In conclusion, there was a high incidence of reduced bone mass among our patients, which was influenced by weight and BMI, by the use and the time of estrogen replacement, and by the presence of spontaneous puberty.

SUMMARYobjectIve. To evaluate the frequency and type of cardiovascular (CV) and renal/collecting system (R/ CS) abnormalities seen in a sample of patients with Turner Syndrome (TS) and to verify the proportion of those anomalies detected only after diagnosis was established. Methods. Retrospective study of 130 patients with TS diagnosed in an outpatient setting between 1989 and 2006. The mean age at diagnosis was 11.9 years. Data were obtained by personal history of CV and R/CS disorders and by results of echocardiogram and ultrasonography of the kidneys and collecting system performed after diagnosis. results. 25.6% of patients who underwent echocardiograms presented CV abnormalities. Among them, mitral regurgitation (21.4%), bicuspid aortic valve (19%) and aortic coarctation (19%) were the most frequent. R/CS anomalies were found in 29.3% of patients who underwent ultrasonography. Among them, duplication of the collecting system and hydronephrosis (25% each) and horseshoe kidney (21.2%) were the most frequent. In about 80% of cases there was no previous knowledge of these anomalies. conclusIon. The frequency of CV and R/CS abnormalities found in this study was similar to that of previous studies, but most were found in routine exams after TS diagnosis. Thus, early detection of associated anomalies depends on early detection of TS.

Glucocorticoids are essential in the treatment of patients with congenital adrenal hyperplasia (CAH). The opposite actions of glucocorticoids and androgens in bone mass achievement justify a study of bone mineral density (BMD) in these patients. We evaluated BMD in patients with CAH due to classic 21-hydroxylase (CYP21A2) deficiency and investigated the involvement of clinical and laboratory factors in the BMD. This study assessed the clinical and laboratory factors involved in BMD of 45 patients at the Pediatric Unit of Endocrinology, UNICAMP, who had been diagnosed as having classical CAH due to CYP21A2 deficiency including molecular characterization. The sample consisted of 28 females and 17 males; 23 salt-wasting (SW) and 22 simple virilizing (SV) cases, with average of 9.9 years (ranges, 5.1-16.3 years) when bone densitometry was performed. The DEXA method was used for calculating the areal BMD Z score in L2-L4. The variables were analyzed with reference to the BMD for chronological age (BMD/CA), height age (BMD/HA), and bone age (BMD/BA). The mean Z score for BMD/CA was 0.08 +/- 1.21 (-2.55 to 2.64); it was 0.29 +/- 1.33 (-2.01 to 4.00) for BMD/HA, and -0.90 +/- 1.24 (-3.41 to 1.92) for BMD/BA. The BMD/CA was significantly lower in females and in patients on treatment for a long period and of more advanced chronological age. Weight and body mass index (BMI) Z scores showed a positive correlation with advanced BA. The higher the weight and BMI Z scores, the higher the BMD/HA. The BMD/BA values were significantly higher in the group in which BA was closer to CA. The BMD/BA value was significantly lower when compared to the value obtained with height and chronological ages. Sex, duration of treatment, weight, BMI, and bone age have an effect on areal BMD in patients with CAH due to CYP21A2 deficiency, which may be underestimated when evaluated in relation to CA and HA.

OBJETIVO: Avaliar o efeito do aprimoramento da análise cromossômica sobre os achados citogenéticos de pacientes com síndrome de Turner (ST). MÉTODOS: Estudo retrospectivo dos resultados de cariótipo de 260 pacientes com ST, com análise das técnicas de bandamento, número de células avaliadas e pesquisa de sequências de cromossomo Y. Segundo o cariótipo, dividiu-se em 45,X; mosaicismo cromossômico sem Y; aberrações estruturais de cromossomos sexuais com ou sem mosaicismo; mosaicismo com cromossomo Y. RESULTADOS: O cariótipo 45,X foi o mais frequente (108), seguido de aberrações estruturais (88) e mosaicismo (58 sem Y e 6 com Y). A introdução de técnicas de bandamento e o aumento do número de células analisadas resultaram em redução progressiva de pacientes 45,X e aumento de aberrações estruturais. O estudo de sequências de cromossomo Y foi feito em 96 casos e foi positivo em 10. CONCLUSÕES: O aperfeiçoamento da análise cromossômica ao longo do tempo modificou o perfil citogenético da ST.

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Objective: To analyze the clinical features of patients with suspected diagnosis of Turner syndrome (TS) in a reference service.Methods: Retrospective analysis of 425 patients: data pertaining to age, height and pubertal stage at diagnosis, as well as the specialty of the physician who referred the patient were collected. Patients with and without TS were compared, as well as those with TS according to specialty of the physician; the correlation between age and height at diagnosis was analyzed.Results: TS diagnosis was made in 36.9% of the cases with a mean age of 12.0 years, and height z score = -3.09; pubertal delay was found in 71.4% of the 63 patients aged more than 13 years. When compared to the other patients, girls with TS had a higher height deficit and higher frequency of pubertal delay. TS patients referred by pediatricians were significantly younger (9.3 years vs. 15.4 years), but their height and frequency of pubertal delay were similar to those referred by nonpediatricians. There was a significant negative linear correlation between age and height in the total amount of patients with TS, but not among those referred by non-pediatricians. Conclusions:Mean age at TS diagnosis is still higher than that observed in developed countries, and the presence of spontaneous pubertal signs and/or less pronounced growth deficit in some cases may contribute to delayed clinical suspicion of TS. Information required for early TS diagnosis must be spread among pediatricians and nonpediatricians.J Pediatr (Rio J). 2010;86(2):121-125: Growth disorders, hypogonadism, chromosome aberrations, early diagnosis. ResumoObjetivo: Analisar as características clínicas de pacientes com suspeita de síndrome de Turner (ST) em um serviço de referência.Métodos: Análise retrospectiva de 425 pacientes. Foram colhidos dados de idade, estatura e estádio puberal no momento do diagnóstico, bem como da especialidade do médico que encaminhou a paciente. Comparação das pacientes com e sem ST e daquelas com ST de acordo com a especialidade e análise de correlação entre estatura e idade ao diagnóstico.Resultados: O diagnóstico de ST foi feito, em 36,9% dos casos, com média de idade de 12,0 anos e escore z da estatura = -3,09; havia atraso puberal em 71,4% das 63 pacientes maiores de 13 anos. Comparadas às demais, as meninas com ST apresentavam maior deficit na estatura e maior frequência de atraso puberal. Pacientes com ST encaminhadas por pediatras eram significativamente mais jovens (9,3 anos versus 15,4 anos), porém com estatura e frequência de atraso puberal semelhantes às daquelas encaminhadas por não pediatras. Houve correlação linear negativa significativa entre idade ao diagnóstico e estatura no total de pacientes com ST, mas não entre as encaminhadas por não pediatras. Conclusões:A média de idade ao diagnóstico da ST ainda é superior àquela dos países desenvolvidos, e a presença de sinais puberais espontâneos e/ou de deficit de crescimento menos acentuado em algumas pacientes pode contribuir para o atraso na suspeita clínica. ...

BackgroundCongenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency.MethodsWe used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study.ResultsAn allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles.ConclusionsThis study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil.