46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features

Baronio, Federico; Ortolano, Rita; Menabò, Soara; Cassio, Alessandra; Baldazzi, Lilia; Natale, Valeria Di; Tonti, Giacomo; Vestrucci, Benedetta; Balsamo, Antonio

doi:10.3390/ijms20184605

Cited by 32 publications

(31 citation statements)

References 231 publications

(344 reference statements)

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“…Less frequent types of CAH are 11β-hydroxylase deficiency ( CYP11B1-D , up to 8% cases), 17α-hydroxylase/17–20 lyase deficiency ( CYP17A1-D ), 3β-hydroxysteroid dehydrogenase deficiency ( HDS3B2-D ), P450 oxidoreductase deficiency (POR-D), P450 cytochrome side-chain cleavage deficiency ( CYP11A1-D ), and StAR deficiency ( StAR-D ). In CYP21A2-D and CYP11B1-D, only adrenal steroidogenesis is affected, whereas a defect in the other enzymes also involves gonadal steroid biosynthesis ( 1 , 2 ) ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…11β-hydroxylase and aldosterone synthase can convert DOC into corticosterone (B). 11-OHD disrupts the synthesis of cortisol with normal production of aldosterone ( 1 ). The key steroid used in diagnosis for the classic form is elevated 11-deoxycortisol basal levels ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

“…A summary of genetic, early clinical, biochemical features, and therapy of the CAH deficiencies presenting in the 1st year of life [modified by(1)]. …”

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confidence: 99%

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Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant

et al. 2020

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Congenital adrenal hyperplasia includes autosomal recessive conditions that affect the adrenal cortex steroidogenic enzymes (cholesterol side-chain cleavage enzyme; 3β-hydroxysteroid dehydrogenase; 17α-hydroxylase/17,20 lyase; P450 oxidoreductase; 21-hydroxylase; and 11β-hydroxylase) and proteins (steroidogenic acute regulatory protein). These are located within the three major pathways of the steroidogenic apparatus involved in the production of mineralocorticoids, glucocorticoids, and androgens. Many countries have introduced newborn screening program (NSP) based on 17-OH-progesterone (17-OHP) immunoassays on dried blood spots, which enable faster diagnosis and treatment of the most severe forms of 21-hydroxylase deficiency (21-OHD). However, in several others, the use of this diagnostic tool has not yet been implemented and clinical diagnosis remains challenging, especially for males. Furthermore, less severe classic forms of 21-OHD and other rarer types of CAHs are not identified by NSP. The aim of this mini review is to highlight both the main clinical characteristics and therapeutic options of these conditions, which may be useful for a differential diagnosis in the neonatal period, while contributing to the biochemical evolution taking place in the steroidogenic field. Currently, chromatographic techniques coupled with tandem mass spectrometry are gaining attention due to an increase in the reliability of the test results of NPS for detecting 21-OHD. Furthermore, the possibility of identifying CAH patients that are not affected by 21-OHD but presenting elevated levels of 17-OHP by NSP and the opportunity to include the recently investigated 11-oxygenated androgens in the steroid profiles are promising tools for a more precise diagnosis and monitoring of some of these conditions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant

et al. 2020

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“…Neonatal screening programmes for CAH have been instituted in Sweden and in many other countries worldwide to facilitate early diagnosis and prevent salt-losing crises and death in neonates [5][6][7]. Consequently, life-long replacement therapy with hydrocortisone (HC) and mineralocorticoid is already started in the second week of life [1,8]. However, because of difficulties in mimicking the normal circadian cortisol rhythm with conventional glucocorticoid (GC) treatment, there is a risk of both over-and under-treatment during an individual's lifespan.…”

Section: Introductionmentioning

confidence: 99%

Good overall behavioural adjustment in children and adolescents with classic congenital adrenal hyperplasia

et al. 2020

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Purpose Patients with classic congenital adrenal hyperplasia (CAH) are treated postnatally with lifelong glucocorticoid (GC) replacement therapy. Although prolonged exposure to GCs may have a negative impact on behaviour, few studies have studied this issue. We therefore investigated behavioural outcomes in male and female children and adolescents with CAH. Methods An observational study in which Swedish and Italian children and adolescents with CAH identified through neonatal screening for CAH (n = 57, age range 7-17 years) were compared with healthy population controls matched for age and sex (n = 72, age range 7-17 years). Thirteen (eight females) of the fifty-seven children and adolescents with CAH had been treated prenatally with dexamethasone (DEX). Standardised questionnaires for parents and self-report scales for children/adolescents were used to assess behavioural and emotional problems, social anxiety, temperament and scholastic competence. Results There were no statistically significant differences between CAH patients (not prenatally treated with DEX) and controls on most of the scales measuring adaptive functioning or behavioural problems. However, children with CAH were rated by their parents to have more social problems than controls (Child Behaviour Checklist, CBCL social problems, p = 0.032). In the small group (n = 13) of prenatally DEX-treated cases parents rated their children/adolescents to have more mood problems compared with non-DEX-treated children/adolescents with CAH (CBCL-withdrawn/depressed, p = 0.019). Conclusion Children/adolescents with CAH showed good overall adjustment. The clinical significance of the parentally perceived increase in social problems in children/adolescents with CAH requires further investigation. The findings underline the importance of psychological support for children/adolescents with a chronic condition.

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“…The clinical course of PORD in adulthood and the long-term consequence for female fertility remain unknown. In theory, the female fertility should be severely impaired by the presence of DSD and disordered steroidogenesis due to reduced activities of three steroidogenic enzymes caused by PORD [10].…”

Section: Introductionmentioning

confidence: 99%

Successful Live Birth in a Chinese Woman with P450 Oxidoreductase Deficiency through Frozen-thawed Embryo Transfer

Pan

Zheng

Chen

et al. 2020

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Background: Congenital adrenal hyperplasia (CAH) caused by P450 oxidoreductase deficiency (PORD) in 46,XX patients is characterized by genital ambiguity, primary amenorrhea, absent or incomplete sexual maturation, infertility, skeletal malformations and so on. But few pregnancies have been reported from these female patients with PORD. Case Description: A 29-year-old Chinese woman with PORD due to the compound heterozygous mutation (c.1370G>A/c.1196_1204del) in the P450 oxidoreductase(POR) gene had suffered from primary amenorrhea and infertility. She had one cancelled cycle of ovulation induction due to low serum estradiol(E2), high progesterone(P) levels and thin endometrium，then in vitro fertilization (IVF) was recommended. At the first IVF cycle, 4 oocytes were retrieved and 4 viable embryos were cryopreserved due to thin endometrium associated with low E2 and prematurely elevated P after ovarian stimulation, even though oral dexamethasone were used to control adrenal P overproduction at the same time. When basal P fell to <1.5ng/ml, artificial endometrial preparation and frozen embryo transfer were performed, resulting in a twin pregnancy. She delivered a healthy boy and a healthy girl by caesarean section at 37 weeks and 2 days of gestation. Conclusions: We report the pregnancy achieved in a CAH woman caused by a compound heterozygous POR mutation, with primary amenorrhea and disorders of steroidogenesis. It seemed that disorders of steroidogenesis caused by PORD didn’t impair the developmental potential of oocytes. IVF and frozen embryo transfer after adequate hormonal control and endometrial preparation should be an effective infertility treatment for PORD women.

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46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features

Cited by 32 publications

References 231 publications

Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant

Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant

Good overall behavioural adjustment in children and adolescents with classic congenital adrenal hyperplasia

Successful Live Birth in a Chinese Woman with P450 Oxidoreductase Deficiency through Frozen-thawed Embryo Transfer

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