Novel nonsense mutation (W302X) in the steroid 21-hydroxylase gene of a Finnish patient with the salt-wasting form of congenital adrenal hyperplasia

Abstract: Congenital adrenal hyperplasia is a group of genetic diseases due to the disablement of 7 genes; one of them is steroid 21-hydroxylase deficiency. The genes of congenital adrenal hyperplasia encode enzymes taking part in the steroidogenesis of adrenal gland. Steroid 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations of the steroid 21-hydroxylase gene. The mutations of steroid 21-hydroxylase gene cause 95% of the congenital adrenal hyperplasia cases. Although the non-classic steroid 21-hydroxylase deficiency with mild symptoms is seldom diagnosed, the classic steroid 21-hydroxylase deficiency may lead to life-threatening salt-wasting and adrenal crises due to the insufficient aldosterone and cortisol serum levels. The classic type requires life-long steroid replacement which may result in cushingoid side effects, and typical comorbidities may be also developed. The patients’ quality of life is decreased, and their mortality is much higher than that of the population without steroid 21-hydroxylase deficiency. The diagnosis, consequences and the patients’ life-long clinical care require a multidisciplinary approach: the specialists in pediatrics, internal medicine, endocrinology, laboratory medicine, genetic diagnostics, surgery, obstetrics-gynecology and psychology need to work together. Orv Hetil. 2018; 159(7): 269–277.

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Concurrence of Meningomyelocele and Salt-Wasting Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Case Reports in Pediatrics ◽

10.1155/2015/196374 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Heves Kırmızıbekmez ◽

Rahime Gül Yesiltepe Mutlu ◽

Serdar Moralıoğlu ◽

Ahmet Tellioğlu ◽

Ayşenur Cerrah Celayir

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Growth Retardation ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Salt Wasting ◽

Significant Regression ◽

One Year ◽

The One ◽

21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a group of inherited defects of cortisol biosynthesis. A case of classical CAH due to 21-hydroxylase deficiency (21-OHD) with early onset of salt waste and concurrence of meningomyelocele (MMC) was presented here. The management of salt-wasting crisis which is complicated by a postrenal dysfunction due to neurogenic bladder was described. Possible reasons of growth retardation in the one-year follow-up period were discussed. A significant regression of the phallus with proper medical treatment was also mentioned.

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Aldosterone Synthesis in Salt-Wasting Congenital Adrenal Hyperplasia with Complete Absence of Adrenal 21-Hydroxylase

New England Journal of Medicine ◽

10.1056/nejm199101173240302 ◽

1991 ◽

Vol 324 (3) ◽

pp. 145-149 ◽

Cited By ~ 66

Author(s):

Phyllis W. Speiser ◽

Levon Agdere ◽

Hajime Ueshiba ◽

Perrin C. White ◽

Maria I. New

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Hyperplasia ◽

Salt Wasting

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The role of imaging in congenital adrenal hyperplasia

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003371 ◽

2014 ◽

Vol 58 (7) ◽

pp. 701-708 ◽

Cited By ~ 6

Author(s):

Sara Reis Teixeira ◽

Paula Condé Lamparelli Elias ◽

Marco Túlio Soares Andrade ◽

Andrea Farias Melo ◽

Jorge Elias Junior

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Tumors ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

Testicular Adrenal Rest Tumors ◽

High Incidence ◽

Adrenal Rest ◽

Hormonal Evaluation

Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.

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High Reliability of Neonatal Screening for Congenital Adrenal Hyperplasia in Switzerland

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-012093 ◽

2002 ◽

Vol 87 (9) ◽

pp. 4106-4110 ◽

Cited By ~ 29

Author(s):

Michael Steigert ◽

Eugen J. Schoenle ◽

Anna Biason-Lauber ◽

Toni Torresani

Keyword(s):

Positive Predictive Value ◽

Congenital Adrenal Hyperplasia ◽

Predictive Value ◽

Neonatal Screening ◽

Screening Program ◽

High Reliability ◽

Dried Blood Spots ◽

Recall Rate ◽

Adrenal Hyperplasia ◽

Salt Wasting

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children’s Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.

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