Navegando por Palavras-chave "21-hydroxylase deficiency"
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- ItemSomente Metadadados21-hydroxylase deficiency transiently mimicking combined 21- and 11 beta-hydroxylase deficiency(Walter De Gruyter Gmbh, 2008-05-01) Tonetto-Fernandes, Vânia [UNIFESP]; Lemos-Marini, Sofia Helena Valente de; Mello, Maricilda Palandi de; Ribeiro-Neto, Luciane Maria [UNIFESP]; Kater, Claudio Elias [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)21-Hydroxylase deficiency (21OHD) is the commonest form of congenital adrenal hyperplasia, while 11 beta OHD represents 5% of cases. Although both result from mutations in distinct genes, cases of 'apparent' combined 210HD and 11 beta OHD (AC21,11OHD) have been occasionally reported. A 6 year-old girl, born with ambiguous genitalia and salt-loss, had serum elevations (ng/dl) of androstenedione (>1,000), 17-hydroxy-progesterone (17OHP; 38,483), 21-deoxycortisol (21DF; 23,338), and 11-deoxycortisol (S; 4,928), suggesting AC21,11OHD. CYP21A and CYP11B1 genotyping identified mutations only in the former. On follow-up, serum S became normal but 17OHP and 21DF were still elevated. ACTH stimulation disclosed elevated levels of 17OHP and 21DF, but unresponsive S and undetectable deoxycorticosterone. The hormonal pattern initially suggested AC21,11OHD, but subsequent normalization of S showed transient 11-hydroxylase inhibition. This may have occurred by enzyme or co-enzyme immaturity or functional discrepancy, but also by selective inhibition of 11 beta-OH by excess intra-adrenal concentration of androgens, acting as pseudo-substrates for this enzyme.
- ItemSomente MetadadadosThe effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia(Wiley-Blackwell, 2013-11-01) Kaupert, L. C.; Lemos-Marini, S. H. V.; Mello, Maricilda Palandi de [UNIFESP]; Moreira, R. P.; Brito, V. N.; Jorge, A. A. L.; Longui, C. A.; Guerra, G.; Mendonca, B. B.; Bachega, T. A.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)The 21-hydroxylase deficiency (21OHD) is caused by CYP21A2 mutations resulting in severe or moderate enzymatic impairments. 21OHD females carrying similar genotypes present different degrees of external genitalia virilization, suggesting the influence of other genetic factors. Single nucleotide variants (SNVs) in the CYP3A7 gene and in its transcription factors, related to fetal 19-carbon steroid metabolism, could modulate the genital phenotype. To evaluate the influence of the 21OHD genotypes and the CYP3A7, PXR and CARSNVs on the genital phenotype in 21OHD females. Prader scores were evaluated in 183 patients. the CYP3A7, PXR and CARSNVs were screened and the 21OHD genotypes were classified according to their severity: severe and moderate groups. Patients with severe genotype showed higher degree of genital virilization (Prader median III, IQR III-IV) than those with moderate genotype (III, IQR II-III) (p<0.001). However, a great overlap was observed between genotype groups. Among all the SNVs tested, only the CAR rs2307424 variant correlated with Prader scores (r(2)=0.253; p=0.023). the CYP21A2 genotypes influence the severity of genital virilization in 21OHD females. We also suggest that the CAR variant, which results in a poor metabolizer phenotype, could account for a higher degree of external genitalia virilization.
- ItemAcesso aberto (Open Access)Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening(Sociedade Brasileira de Endocrinologia e Metabologia, 2008-11-01) Soardi, Fernanda Caroline; Lemos-Marini, Sofia Helena Valente de; Coeli, Fernanda Borchers; Maturana, Víctor Gonçalves; Silva, Márcia Duarte Barbosa da; Bernardi, Renan Darin; Justo, Giselle Zenker [UNIFESP]; Mello, Maricilda Palandi de; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)Steroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17-hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that healthy preterm infants have high levels of 17-OHP resulting in false positive cases. We report on molecular features of a boy born pre-term (GA = 30 weeks; weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon neonatal screening who was treated as having CAH up to the age of 8 months. He was brought to us for molecular diagnosis. Medication was gradually suspended and serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound heterozygous status with a group of nucleotide alterations located at the 3' end intron 4 and 5' end exon 5 corresponding to the splice site acceptor region. Molecular studies continued in order to exclude the possibility of a nonclassical 21-OHD form. The group of three nucleotide changes was demonstrated to be a normal variant since they failed to interfere with the normal splicing process upon minigene studies.
- ItemAcesso aberto (Open Access)Hiperplasia adrenal congênita em mulheres adultas: manejo de antigos e novos desafios(Sociedade Brasileira de Endocrinologia e Metabologia, 2014-03-01) Costa-Barbosa, Flávia A.; Telles-Silveira, Mariana; Kater, Claudio Elias [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Due to major improvements in the management and therapy of patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency (21OHD) along childhood and adolescence, affected women are able to reach adulthood. Therefore, management throughout adult life became even more complex, leading to new challenges. Both the protracted use of corticosteroids (sometimes in supraphysiologic doses), and excess androgen (due to irregular treatment and/or inadequate dosage) may impair the quality of life and health outcomes in affected adult women, causing osteoporosis, metabolic disturbances with high cardiovascular risk, cosmetic damage, infertility, and psychosocial and psychosexual changes. However, long-term follow-up studies with 21OHD adult women are still required. In this review, we discuss some important and controversial aspects of the follow-up of adult women with 21OHD, and recommend the use of a customized multi-disciplinary therapeutic approach while further studies with these patients do not provide distinct understanding and well-defined attitudes towards better quality of life.
- ItemAcesso aberto (Open Access)Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency(Faculdade de Medicina / USP, 2011-01-01) Moreira, Ricardo P. P.; Jorge, Alexander A. L.; Gomes, Larissa G.; Kaupert, Laura C.; Massud Filho, João [UNIFESP]; Mendonca, Berenice B.; Bachega, Tania Aparecida Sartori Sanchez; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)INTRODUCTION: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed. OBJECTIVE: The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. METHODS: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels. RESULTS: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose. CONCLUSION: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.