Clinical And Laboratory Profile Of Pediatric And Adolescent Patients With Type 1 Diabetes

Objective: To evaluate clinical and laboratory profiles of patients with type 1 diabetes mellitus in three public hospitals in São Paulo, Brazil, since type 1 diabetes mellitus is a chronic illness that occurs mainly in the pediatric age group in the Brazilian population. Methods: Cross-sectional study with patients followed up in reference centers in São José do Rio Preto (FAMERP), Campinas (UNICAMP) and São Paulo (Conjunto Hospitalar do Mandaqui). Data about gender, age, diabetes duration, daily insulin dose, number of daily insulin injections, and glycosylated hemoglobin (HbA1c) were analyzed. Results: Two hundred and thirty-nine patients (131 females) were evaluated; mean age was 13.1±4.7 years and mean diabetes duration was 6.6±4.2 years. Daily insulin doses ranged from 0.1 to 1.78 units/kg/day (0.88±0.28), and 180 (74.7%) patients had two daily injections. HbA 1c ranged from 4.6 to 17.9% (10.0±2.3%). Conclusions: Although the hospitals included in this study are excellence centers for the follow-up of patients with diabetes in three municipalities in the state of São Paulo, one of the most developed states in Brazil, blood glucose control evaluated according to HbA1c was not adequate. Findings confirm that, despite the efforts of all the professionals involved, great challenges still lie ahead. Copyright © 2009 by Sociedade Brasileira de Pediatria.856490494Karvonen, M., Viik-Kajander, M., Moltchanova, E., Libman, I., LaPorte, R., Tuomilehto, J., Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group (2000) Diabetes Care, 23, pp. 1516-1526Hoey, H., Aanstoot, H.J., Chiarelli, F., Daneman, D., Danne, T., Dorchy, H., Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes (2001) Diabetes Care, 24, pp. 1923-1928Danne, T., Mortensen, H.B., Hougaard, P., Lynggaard, H., Aanstoot, H.J., Chiarelli, F., Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group (2001) Diabetes Care, 24, pp. 1342-1347The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-86Schmid, H., New options in insulin therapy (2007) J Pediatr (Rio J), 83, pp. S146-S154Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. Group. J Pediatr. 1994;125:177-88Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group (1991) Am J Med, 90, pp. 450-459Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group (1997) Diabetes, 46, pp. 271-286Malerbi, D., Damiani, D., Rassi, N., Chacra, A.R., Niclewicz, E.D., Silva Filho, R., Posição de consenso da Sociedade Brasileira de Diabetes - Insulinoterapia intensiva e terapêutica com bombas de insulina. (2006) Arq Bras Endocrinol Metab, 50, pp. 125-135Rewers, M., Pihoker, C., Donaghue, K., Hanas, R., Swift, P., Klingensmith, G.J., Assessment and monitoring of glycemic control in children and adolescents with diabetes (2007) Pediatr Diabetes, 8, pp. 408-418Nathan, D.M., Cleary, P.A., Backlund, J.Y., Genuth, S.M., Lachin, J.M., Orchard, T.J., Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes (2005) N Engl J Med, 353, pp. 2643-2653Mortensen, H.B., Robertson, K.J., Aanstoot, H.J., Danne, T., Holl, R.W., Hougaard, P., Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvidøre Study Group on Childhood Diabetes (1998) Diabet Med, 15, pp. 752-759Mendes, A.B., Fittipaldi, J.A., Neves, R.C., Chacra, A.R., Moreira Jr., E.D., Prevalence and correlates of inadequate glycaemic control: Results from a nationwide survey in 6,671 adults with diabetes in Brazil (2009) Acta Diabetol, , In pressEliaschewitz, F.G., Franco, D.R., Does brittle diabetes exist as a clinical entity? Arq Bras Endocrinol (2009) Metabol, 53, pp. 466-469Akbaş, S., Karabekiroǧlu, K., Ozgen, T., Tasdemir, G., Karakurt, M., Senses, A., Association between emotional and behavioral problems and metabolic control in children and adolescents with Type 1 diabetes (2009) J Endocrinol Invest, 32, pp. 325-329Grossi, S.A., Lottenberg, S.A., Lottenberg, A.M., Della Manna, T., Kuperman, H., Home blood glucose monitoring in type 1 diabetes mellitus (2009) Rev Lat Am Enfermagem, 17, pp. 194-200Crasto, W., Jarvis, J., Khunti, K., Davies, M.J., New insulins and new insulin regimens: A review of their role in improving glycaemic control in patients with diabetes (2009) Postgrad Med J, 85, pp. 257-26

21-hydroxylase Deficiency Transiently Mimicking Combined 21- And 11β-hydroxylase Deficiency

21-Hydroxylase deficiency (21OHD) is the commonest form of congenital adrenal hyperplasia, while 11βOHD represents 5% of cases. Although both result from mutations in distinct genes, cases of 'apparent' combined 21OHD and 11βOHD (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 (170HP; 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 170HP and 21DF were still elevated. ACTH stimulation disclosed elevated levels of 170HP 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 or curred by enzyme or co-enzyme immaturity or functional discrepancy, but also by selective inhibition of 11β-OH by excess intra-adrenal concentration of androgens, acting as pseudo-substrates for this enzyme. © Freund Publishing House Ltd., London.215487494Holcombe, J.H., Keenan, B.S., Nichols, B.L., Kirkland, R.T., Clayton, G.W., Neonatal salt loss in the hypertensive form of congenital adrenal hyperplasia (1980) Pediatrics, 65, pp. 777-780Zachmann, M., Tassinari, D., Prader, A., Clinical and biochemical variability of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. A study of 25 patients (1983) J Clin Endocrinol Metabol, 56, pp. 222-229Fiet, J., Boudi, A., Giton, F., Villette, J.M., Boudou, P., Soliman, H., Morineau, G., Galons, H., Plasma 21-deoxycortisol: Comparison of a time-resolved flubro-immunoassay using a biotinylated tracer with a radio-immunoassay using 125-iodine (2000) J Steroid Biochem Mol Biol, 72, pp. 55-60Gandy, H.M., Keutmann, E.H., Izzo, A.J., Characterization of urinary steroids in adrenal hyperplasia: Isolation of metabolites of cortisol, compound S, and deoxycorticosterone from a normotensive patient with adrenogenital syndrome (1960) J Clin Invest, 39, pp. 364-377Maschler, I., Weidenfeld, J., Muller, A., Slavin, S., Shaefer, J., Chovers, J., Finkelstein, M., A case of adrenogenital syndrome with aberrant 11β-hydroxylation (1977) Acta Endocrinol (Copenh), 85, pp. 832-830Fukushima, D.K., Nishina, T., Wu, R.H.K., Hellman, L., Finkelstein, J.W., Rapid assay of plasma 21-deoxy-cortisol and 11-deoxycortisol in congenital adrenal hyperplasia (1979) Clin Endocrinol, 10, pp. 367-375Kolanowski, J., Crabbe, J., Defective 11β-hydroxylation in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (1981) Ann Endocrinol (Paris), 42, pp. 537-538Finkelstein, M., Litvin, Y., Mizrachi, Y., Neiman, G., Rosler, A., Apparent double defect in C11β- and C21-steroid hydroxylation in congenital adrenal hyperplasia (1983) J Steroid Biochem, 19, pp. 675-681Hurwitz, A., Brautbar, C., Milwidsky, A., Vecsei, P., Milewitz, A., Navot, D., Rosler, A., Combined 21- and 11β-hydroxylase deficiency in familial congenital adrenal hyperplasia (1985) J Clin Endocrinol Metabol, 60, pp. 631-637Penny, R., Vecsei, P., Congenital adrenal hyperplasia due to combined 21- and 11β-hydroxylase deficiency (1989) J Endocrinol Invest, 12, pp. 723-728Gillis, D., Speiser, P., Zhou, Z., Rolsler, A., Combined 21-hydroxylase and 11β-hydroxylaoe deficiency: Patient report and molecular basis (2000) J Pediatr Endocrinol Metab, 13, pp. 945-949Fernandes, V.T., Ribeiro-Neto, L.M., Vieira, J.G.H., Verreschi, I.T.N., Fiet, J., Kater, C.E., Radioimmunoassay for serum 21-deoxycortisol and its clinical application in congenital adrenal hyperplasia (2003) Arq Bras Endocrinol Metab, 47, pp. 171-176. , in PortugueseFernandes, V.T., Ribeiro-Neto, L.M., Lima, S.B., Vieira, J.G.H., Verreschi, I.T.N., Kater, C.E., Reversed-phase high-performance liquid chromatography separation of adrenal steroids prior to radioimmunoassay: Application in congenital adrenal hyperplasia (2003) J Chromatog Sci, 41, pp. 251-254Paulino, L.C., Araujo, M., Guerra Jr, G., Marini, S.H., De Mello, M.P., Mutation distribution and CYP21/C4 locus variability in Brazilian families with the classical form of the 21-hydroxylase deficiency (1999) Acta Paediatr, 88, pp. 275-283Wilson, R.C., Wei, J.Q., Cheng, K.C., Mercado, A.B., New, M.I., Rapid deoxyribonucleic acid analysis by allele-specific polymerase chain reaction for detection of mutations in the steroid 21-hydroxylase gene (1995) J Clin Endocrinol Metab, 80, pp. 1635-1640De Carvalho, C.E., Castro, M., Moreira, A.C., de Mello, M.P., CYP11B1 intragenic polymorphisms give evidence for a different Q356X allele in an Afican-Brazilian patient (1999) J Endocr Genet, 1, pp. 79-86White, P.C., Speiser, P.W., Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (2000) Endocr Rev, 21, pp. 245-291Carroll, M.C., Palsdottir, A., Belt, K.T., Porter, R.R., Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region (1985) EMBO J, 4, pp. 2547-2552Donohoue, P.A., Van Dop, C., McLean, R.H., White, P.C., Jospe, N., Migeon, C.J., Gene conversion in salt-losing congenital adrenal hyperplasia with absent complement C4B protein (1986) J Clin Endocrinol Metab, 62, pp. 995-1002Grischuk, Y., Rubtsov, P., Riepe, F.G., Grötzinger, J., Beljelarskaia, S., Prasgolov, V., Kalintchenko, N., Krone, N., Four novel missense mutations in the CYP21A2 gene detected in Russian patients suffering from the classical form of congenital adrenal hyperplasia: Identification, functional characterization, and structural analysis (2006) J Clin Endocrinol Metab, 91, pp. 4976-4980Tonetto-Fernandes, V., Lemos-Marini, S.H.V., Kuperman, H., Ribeiro-Neto, L.M., Verreschi, I.T.N., Kater, C.E., Serum 21-deoxycortisol, 17-hydroxyprogesteione, and 11-deoxycortisol in classic congenital adrenal hyperplasia: Clinical and hormonal correlations and identification of patients with 11β-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency (2006) J Clin Endocrinol Metab, 91, pp. 2179-2184Fukami, M., Hasegawa, T., Horikawa, I., Ohashi, T., Nishimura, G., Homma, K., Ogata, T., Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and/or aromatase deficiency: Diagnostic value of urine steroid hormone analysis (2006) Pediatr Res, 59, pp. 276-280Flück, C.E., Tajima, T., Pandey, A.V., Arlt, W., Okuhara, K., Verge, C.F., Jabs, E.W., Miller, W.L., Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome (2004) Nat Genet, 36, pp. 228-230Arlt, W., Walker, E.A., Draper, N., Ivison, H.E., Ride, J.P., Hammer, F., Chalder, S.M., Schackleton, C.H., Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: Analytical study (2004) Lancet, 363, pp. 2128-2135Dall'Asta, C., Barbetta, L., Lib, Passini, E., Ambrosi, B., Coexistence of 21-hydroxylase and 11β-hydroxylase deficiency in adrenal incidentalomas. and in subclinical Cushing's syndrome (2002) Horm Res, 57, pp. 192-196Hornsby, P.J., Regulation of 21-hydroxylase activity by steroids in cultured bovine adrenocortical cells: Possible significance for adrenocortical androgen synthesis (1982) Endocrinology, 111, pp. 1092-1101Kater, C.E., Czepielewski, M.A., Biglieri, E.G., Androgen-and estrogen-producing adrenocortical tumors causing hypertension (1990) Endocrine Hypertension, pp. 195-206. , Biglieri EG, ed, New York: Raven PressKater, C.E., Tonetto-Fernandes, V.F., Ribeiro-Neto, L.M., Lemos-Marini, S., Kuperman, H., Partial inhibition of 11β-hydroxylation in the classic 21-hydroxylase deficiency form of congenital adrenal hyperplasia (2004) 86th Annual Meeting of The Endocrine Society, 272. , Abst P 1-476Namiki, M., Koh, E., Meguro, N., Kondoh, N., Kiyohara, H., Okuyama, A., Sakoda, S., Sonoda, T., Extraadrenal expression of steroid 21-hydroxylase and 11β-hydroxylase by a benign testicular Leydig cell tumor (1991) J Steroid Biochem Mol Biol, 39, pp. 897-90

Growth And Body Composition In Children With Type 1 Diabetes Mellitus [crescimento E Composição Corporal De Crianças Com Diabetes Mellitus Tipo 1]

Objective: To evaluate the growth and body composition of pre-pubertal diabetic children, and to check for influence of the age of diabetes onset and length, sex, insulin requirement and glycosylated hemoglobin. Patients and methods: 59 diabetic children (39 M; 29 F), age 1.2-11.5 years, and 67 controls (36 M; 31 F), age 1.2-11.7 years were included. Weight, height, body mass index (BMI), arm circumference, skin folds, fat mass and muscle areas were evaluated and transformed into standard deviation scores (SDS). Results: Among the diabetic children the mean height SDS was -0.13 (± 0.97) while in the control group it was 0.28 (± 0.86) (p= 0.013). The difference between the first and the current height SDS showed that the height SDS decreased significantly (p< 0.001) and multiple regression analysis indicated correlation with the duration of the disease. The mean arm fat SDS also revealed difference (p< 0.001). The means for weight, BMI, addition of 3 skinfolds and muscle mass did not demonstrate difference between the groups. Conclusions: The diabetic children showed reduction of height SDS during the period studied and they were significantly shorter than the controls, even though their statures were within the population standards. The arm fat area also showed to be increased in relation with the controls.503490498Manna, T.D., Damiani, D., Dichtchekenian, V., Setian, N., Diabetes Mellitus na Infância e na Adolescência (2004) Endocinologia Pediátrica, 2a Ed., pp. 195-241. , Setian N, editora. São Paulo: SarvierSilva Jr., G.R., Fuks, A.G., Cunha, E.F., Clemente, E.L.S., Gomes, M.B., Inter-relação de variáveis demográficas, terapêutica insulínica e controle glicêmico em pacientes com diabetes mellitus do tipo 1 atendidos em um hospital universitário (1999) Arq Bras Endocrinol Metab, 43, pp. 114-120Ferreira, S.R.G., Franco, L.J., Vivolo, M.A., Negrato, C.A., Simões, A.C.P., Ventureli, C.R., Population based incidence of IDDM in the state of São Paulo, Brazil (1993) Diabetes Care, 16, pp. 701-704Maia, F.F.R., Araújo, L.R., Síndrome de Mauriac: Forma rara do diabetes mellitus tipo 1 (2002) Arq Bras Endocrinol Metab, 46, pp. 310-315Herber, S.M., Dunsmore, I.R., Does control affect growth in diabetes mellitus? (1988) Acta Paediatr Scand, 77, pp. 303-305Cunha, E.F., Silva Jr., G.R., Clemente, E.L.S., Gomes, M.B., Crescimento de crianças diabéticas em controle ambulatorial em hospital universitário (1999) Arq Bras Endocrinol Metab, 43, pp. 344-350Dunger, D.B., Edge, J.E., Ahmed, M.L., Diabetes mellitus and growth (1995) Curr Opin Endocrinol Diab, 2, pp. 97-104Rodrigues, T.M.B., Silva, I.N., Estatura final de pacientes com Diabetes Mellitus tipo 1 (2001) Arq Bras Endocrinol Metab, 45, pp. 108-114Dunger, D., Ahmed, L., Ong, K., Growth and body composition in type 1 Diabetes Mellitus (2002) Horm Res, 58, pp. 66-71Clinical Pratice Recomendation 2003 (2003) Diabetes Care, 26, pp. S5-20(2004) A Importância Da HbGli (A1c) para a Avaliação Do Controle Glicêmico Em Pacientes Com Diabetes Mellitus: Aspectos Clínicos e Laboratoriais, , Posicionamento Oficial das Sociedades Brasileiras de Endocrinologia e Metabologia, de Patologia Clínica, de Diabetes, da Associaçã o Latino-Americana de Diabetes e da Federação Nacional das Associações e Entidades de Diabetes, São PauloLohman, T.G., Roche, A.F., Martorell, R., (1988) Anthropometric Standardization Reference Manual, , Illinois: Human Kinetics BooksFrisancho, A.R., (1993) Anthropometric Standards for the Assessment of Growth and Nutritional Status, , Michigan: University of Michigan PressKuczmarski, R.J., Ogden, C.L., Grummer-Strawn, L.M., Flegal, K.M., Mei, Z., Guo, S., CDC growth charts: United States (2000) Adv Data, 8, pp. 1-27Ogden, C.L., Kuczmarski, R.J., Flegal, K.M., Mei, Z., Guo, S., Wei, R., Centers for Disease Control and Prevention 2000 growth charts for the United States: Improvements to the 1977 National Center for Health Statistics version (2002) Pediatrics, 109, pp. 45-60Goran, M.I., Kaskoun, M.C., Carpenter, W.H., Poehlman, E.T., Ravussin, E., Fontvieille, A.M., Estimating body composition of young children by using bioeletrical resistance (1993) J Appl Physiol, 75, pp. 1776-1780Fomon, S., Hanschke, F., Ziegler, E., Nelson, B., Body composition of reference children from birth to age 10 years (1982) Am J Nutr, 35, pp. 1169-1175Danne, T., Kordonouri, O., Enders, I., Weber, B., Factors influencing height and weight development in children with diabetes - Results of the Berlin retinopathy study (1997) Diabetes Care, 20, pp. 281-285Petersen, H.D., Korsgaard, B., Deckert, T., Nielsen, E., Growth, body weight and insulin requirement in diabetic children (1978) Acta Paediatr Scand, 67, pp. 453-457Thon, A., Heinze, E., Feilen, K.D., Holl, R.W., Schmidt, H., Koletzko, S., Development of height and weight in children with diabetes mellitus: Report on two prospective multicentre studies, one cross-sectional, one longitudinal (1992) Eur J Pediatr, 151, pp. 258-262Malone, J.I., Growth and sexual maturation in children with insulin-dependent diabetes mellitus (1993) Curr Opin Pediatr, 5, pp. 494-498Ozuna, B., Aruza, A., Belgorosky, A., Mazza, C., Estudio del crecimiento en niños com diabetes insulino dependente. Efectos del control metabólico (1995) Med Infant, 2, p. 147Sepúlveda, Z.N., Jaime Perez, C., Iris Mella, G., Crecimiento en niños con diabetes mellitus insulino-dependente (1997) Rev Chil Pediatr, 68, pp. 61-65The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus (1993) N Engl J Med, 329, pp. 977-986Pitukcheewanont, P., Alemzadeh, R., Jacobs, W.R., Jones, B.H., Eberle, A.J., Does glycemic control affect growth velocity in children with insulin-dependent diabetes mellitus (1995) Acta Diabetol, 32, pp. 148-152Salerno, M.C., Argenziano, A., Di Maio, S., Gasparini, N., Formicola, S., De Fellipo, G., Puberal growth, sexual maturation, and final height in children with IDDM (1997) Diabetes Care, 20, pp. 721-723Bognetti, E., Riva, M.C., Bonfanti, R., Meschi, F., Viscardi, M., Chiumello, G., Growth changes in children and adolescents with short-term diabetes (1998) Diabetes Care, 21, pp. 1226-1229Lebl, J., Schober, E., Zidek, T., Baldis, S., Rami, B., Pruhova, S., Growth data in large series of 587 children and adolescents with type 1 diabetes mellitus (2003) Endocr Regul, 37, pp. 153-161Meira, S.O., Morcillo, A.M., Lemos-Marini, S.H.V., Paulino, M.F.V.M., Minicucci, W.J., Guerra Jr., G., Crescimento puberal e altura final em 40 pacientes com diabetes mellitus tipo 1 (2005) Arq Bras Endocrinol Metab, 49, pp. 396-402Brown, M., Ahmed, M.L., Clayton, K.L., Dunger, D.B., Growth during childhood and final height in type 1 diabetes (1994) Diabetic Medicine, 11, pp. 182-187Zachrisson, I., Brismar, K., Hall, K., Wallensteen, M., Dahlqvist, G., Determinants of growth in diabetic pubertal subjects (1997) Diabetes Care, 20, pp. 1261-1265Scheffer-Marinus, P.D., Links, T.P., Reitsma, W.D., Drayer, N.M., Increased height in diabetes mellitus corresponds to the predicted and the adult height (1999) Acta Paediatr, 88, pp. 384-388Castro, J.C., Goulart, E.M.A., Camargos, A.F., Chagas, A.J., Avaliação antropométrica e bioquímica de crianças e adolescentes com diabetes do tipo 1 comparados a um grupo de não diabéticos de mesmo nível sócioeconômico (2000) Arq Bras Endocrinol Metab, 44, pp. 502-508Tattersall, R.B., Pyke, D.A., Growth in diabetic children: Studies in identical twins (1973) Lancet, 17, pp. 1105-1109Pietilläinen, K.H., Virtanen, S.M., Rissanen, A., Rita, H., Mäenpää, A., Diet, obesity, and metabolic control in girls with insulin dependent diabetes mellitus (1995) Arch Dis Child, 73, pp. 398-402Du Caju, M.V.L., Rooman, R.P., Beeck, L.O., Longitudinal data on growth and final height in diabetic children (1995) Pediatr Res, 38, pp. 607-611Ferrante, E., Pitzalis, G., Vania, A., Angelis, P., Guidi, R., Fontana, L., Stato nutrizionale, obesità ed equilibrio metabolico in soggetti in età evolutiva affeti da diabete mellito di tipo 1 (1999) Minerva Pediatr, 51, pp. 39-46Ingberg, C.M., Sarnblad, S., Palmer, M., Schvarez, E., Berne, C., Amont, T., Body composition in adolescent girls with type 1 diabetes. Diabetes UK (2003) Diabet Med, 20, pp. 1005-1011Villalpando, S., Hermida, I., Esquivel, S., Ramos, L., Barrón, C., Pérez-Pasten, E., Growth and body composition measured by anthropometry in healthy and diabetic children (1984) Rev Invest Clin (Mex), 36, pp. 321-32

Structural Aspects Of The P.p222q Homozygous Mutation Of Hsd3b2 Gene In A Patient With Congenital Adrenal Hyperplasia [aspectos Estruturais Da Mutação Homozigótica P.p222q Do Gene Hsd3b2 Em Um Paciente Com Hiperplasia Congênita Da Adrenal]

Type II 3β-hydroxysteroid dehydrogenase/D5-D4-isomerase (3β-HSD2), encoded by the HSD3B2 gene, is a key enzyme involved in the biosynthesis of all the classes of steroid hormones. Deleterious mutations in the HSD3B2 gene cause the classical deficiency of 3β-HSD2, which is a rare autosomal recessive disease that leads to congenital adrenal hyperplasia (CAH). CAH is the most frequent cause of ambiguous genitalia and adrenal insufficiency in newborn infants with variable degrees of salt losing. Here we report the molecular and structural analysis of the HSD3B2 gene in a 46, XY child, who was born from consanguineous parents, and presented with ambiguous genitalia and salt losing. The patient carries a homozygous nucleotide c.665C>A change in exon 4 that putatively substitutes the proline at codon 222 for glutamine. Molecular homology modeling of normal and mutant 3β-HSD2 enzymes emphasizes codon 222 as an important residue for the folding pattern of the enzyme and validates a suitable model for analysis of new mutations. © ABE&M todos os direitos reservados.548768774Simard, J., Durocher, F., Mebarki, F., Turgeon, C., Sanchez, R., Labrie, Y., Molecular biology and genetics of the 3b-hydroxysteroid dehydrogenase/D5-D4 isomerase gene family (1996) J Endocrin, 150, pp. S189-S207Labrie, F., Simard, J., Luu-The, V., Belanger, A., Pelletier, G., Structure, function and tissue-specific gene expression of 3b-hydroxysteroid dehydrogenase/D5-D4 isomerase enzymes in classical and peripheral intracrine steroidogenic tissues (1992) J Steroid Biochem Molec Biol, 43, pp. 805-826Thomas, J., Duax, W., Addlagatta, A., Brandt, S., Fuller, R., Norris, W., Structure/function relationships responsible for coenzyme specificity and the isomerase activity of human type 1 3 beta-hydroxysteroid dehydrogenase/isomerase (2003) J Biol Chem, 12 (37), pp. 35483-35490McBride, M., McVie, A., Burridge, S., Brintnell, B., Craig, N., Wallace, A., Cloning, expression, and physical mapping of the 3β-hydroxysteroid dehydrogenase gene cluster (HSD3BP1-HSD3BP5) in human (1999) Genomics, 61, pp. 277-284Lachance, Y., Luu-The, V., Verreault, H., Dumont, M., Rheaume, E., Leblanc, G., Structure of the human type II 3β-hydroxysteroid dehydrogenase/Δ5- Δ4 isomerase (3β-HSD) gene: Adrenal and gonadal specifity (1991) DNA and Cell Biol, 10, pp. 701-711Rheaume, E., Lachance, Y., Zhao, H., Breton, N., Dumont, M., de Launoit, Y., Structure and expression of a new complementary DNA encoding the almost exclusive 3β-hydroxysteroid dehydrogenase/ Δ5-Δ4 isomerase in human adrenals and gonads (1991) Mol Endocrinol, 8, pp. 1147-1157Rainey, W., Parker, C., Rehman, K., Carr, B., The adrenal genetic puzzle: How do the fetal and adult pieces differ? (2002) Endocr Res, 28 (4), pp. 611-622Rheaume, E., Simard, J., Morel, Y., Mebarki, F., Zachmann, M., Forest, M., Congenital adrenal hyperplasia due to point mutations in the type II 3β-hydroxysteroid dehydrogenase gene (1992) Nature Gen, 1, pp. 239-245Simard, J., Rheaume, E., Sanchez, R., Laflamme, N., Launoit, Y., Luu--the, V., Molecular basis of congenital adrenal hyperplasia due to 37beta;-hydroxysteroid dehydrogenase deficiency (1993) Mol Endocrinol, 7, pp. 716-728Pang, S., Congenital adrenal hyperplasia owing to 3β-hydroxysteroid dehydrogenase deficiency (2001) Endocrinol Metab Clin North Am, 1, pp. 81-99Simard, J., Moisan, A., Morel, Y., Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase deficiency (2002) Semin Reprod Med, 3, pp. 255-276Pang, S., Lerner, A.J., Stoner, E., Levine, L.S., Oberfield, S.E., Engel, I., Late-onset adrenal steroid 3 beta-hydroxysteroid dehydrogenase deficiency. I. 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Central Precocious Puberty As A Sole Manifestation Of Suprasellar Arachnoid Cyst [puberdade Precoce Central Como única Manifestação De Cisto Aracnoide Supraselar]

Objective: Arachnoid cysts (AC) are a rare finding; 10% of them are suprasellar and occur almost exclusively in children. They are frequently associated with neurological and visual manifestations. Central precocious puberty as a sole manifestation is uncommon.Case description: Girl evaluated at the age of two years and seven months. She started breast development at the age of one year and eight months, pubic and axillary hair at the age of two years, with growth velocity acceleration (13cm/year) and increased bone age (seven years and one month). On exam: weight: 22.6kg (Z+4.0), height: 106cm (Z+3.5) and puberal stage of B3P2. The GnRH stimulus test was performed (basal LH 8.3 IU/L, at 30 minutes 94.3 IU/L; FSH basal=10.1 IU/L, at 30 minutes 29.5 IU/L). Nuclear Magnetic Resonance of the skull showed a suprasellar arachnoid cyst. Others stimulation tests were performed and excluded pituitary deficiencies. Treatment with a GnRH analog was started. At the age of four years and three months, she was B3P2, with normal growth velocity and neurologic development. Comments: Central precocious puberty can be the only manifestation of AC. It is essential to establish early diagnosis and treatment. A prolonged follow up is recommended, since late pituitary dysfunctions can occur.291126129Parent, A.S., Rasier, G., Gerard, A., Heger, S., Roth, C., Mastronardi, C., Early onset of puberty: Tracking genetic and environmental factors (2005) Horm Res, 64, pp. 41-47Trivin, C., Couto-Silva, A.C., Sainte-Rose, C., Chemaitilly, W., Kalifa, C., Doz, F., Presentation and evolution of organic central precocious puberty according to the type of CNS lesion (2006) Clin Endocrinol, 65, pp. 239-245Starzyk, J., Kwiatkowski, S., Urbanowicz, W., Starzyk, B., Harasiewicz, M., Kalicka-Kasperczyk, A., Suprasellar arachnoidal cyst as a cause of precocious puberty--report of three patients and literature overview (2003) J Pediatr Endocrinol Metab, 16, pp. 447-455Herter, L.D., Golendziner, E., Flores, J.A., Becker Jr., E., Spritzer, P.M., Ovarian and uterine sonography in healthy girls between 1 and 13 years old: Correlation of findings with age and pubertal status (2002) AJR Am J Roentgenol, 178, pp. 1531-1536Güzel, A., Trippel, M., Ostertage, C.B., Suprasellar arachnoid cyst: A 20-year follow-up after stereotactic internal drainage: Case report and review of the literature (2007) Turk Neurosurg, 17, pp. 211-218Ichiyama, T., Hayashi, T., Nishikawa, M., Furukawa, S., Optic nerve hypoplasia with hypopituitarism and an arachnoid cyst (1996) Brain Dev, 18, pp. 234-235Huang, H.P., Tung, Y.C., Tsai, W.Y., Kuo, M.F., Peng, S.F., Arachnoid cyst with GnRH- dependent sexual precocity and growth hormone deficiency (2004) Pediatr Neurol, 30, pp. 143-145Longas, A.F., Mayayo, E., Labarta, J.L., Congenital growth hormone deficiency arising from central cranial malformations: Experience in KIGS (1999) Growth Hormone Therapy In KIGS - 10 Years' Experience, pp. 135-146. , In: Ranke M, Wilton P, editors, Leipizig: JAB VerlagMohn, A., Schoof, E., Fahlbusch, R., Wenzel, D., Dörr, H.G., The endocrine spectrum of arachnoid cysts in childhood (1999) Pediatr Neurosurg, 31, pp. 316-321Adan, L., Bussières, L., Dinand, V., Zerah, M., Pierre-Kahn, A., Brauner, R., Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst (2000) Eur J Pediatr, 159, pp. 348-355Rivarola, M.A., Belgorosky, A., Mendilaharzu, H., Vidal, G., Precocious puberty in children with tumours of the suprasellar and pineal areas: Organic central precocious puberty (2001) Acta Paediatr, 90, pp. 751-756Golash, A., Mitchell, G., Mallucci, C., May, P., Pilling, D., Prenatal diagnosis of suprasellar arachnoid cyst and postnatal endoscopic treatment (2001) Childs Nerv Syst, 17, pp. 739-742Fujimura, J., Shima, Y., Arai, H., Ogawa, R., Fukunaga, Y., Management of a suprasellar arachnoid cyst identified using prenatal sonography (2006) J Clin Ultrasound, 34, pp. 92-94Ersahin, Y., Kesikci, H., Rüksen, M., Aydin, C., Mutluer, S., Endoscopic treatment of suprasellar arachnoid cysts (2008) Childs Nerv Syst, 24, pp. 1013-1020Dodd, R.L., Barnes, P.D., Huhn, S.L., Spontaneous resolution of a prepontine arachnoid cyst. Case report and review of the literature (2002) Pediatr Neurosurg, 37, pp. 152-157Shim, K.W., Lee, Y.H., Park, E.K., Park, Y.S., Choi, J.U., Kim, D.S., Treatment option for arachnoid cysts (2009) Childs Nerv Syst, 25, pp. 1459-1466Oberbauer, R.W., Haase, J., Pucher, R., Arachnoid cysts in children: A European co-operative study (1992) Childs Nerv Syst, 8, pp. 281-28