Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders, which are usually due to inactivating mutations in single enzymes involved in adrenal steroid biosynthesis. The characteristics of the biochemical and clinical phenotype depend on the specific enzymatic defect. In 21-hydroxylase and 11beta-hydroxylase deficiency only adrenal steroidogenesis is affected, whereas a defect in 3beta-hydroxysteroid dehydrogenase or 17alpha-hydroxylase also involves gonadal steroid biosynthesis. Recently, mutations in the electron donor enzyme P450 oxidoreductase were identified as the cause of CAH with apparent combined 17alpha-hydroxylase and 21-hydroxylase deficiency, thereby illustrating the impact of redox regulation enzymes on steroidogenesis. P450 oxidoreductase deficiency (ORD) has a complex phenotype including two unique features not observed in any other CAH variant, skeletal malformations and severe genital ambiguity in both sexes. Despite invariably low circulating androgens, females with ORD may present with virilized genitalia and mothers may suffer from virilization during pregnancy. This apparently contradictory finding may be explained by the existence of an alternative pathway in human androgen biosynthesis, with important implications for physiology and pathophysiology. This review discusses the biochemical and clinical presentation and the genetic and functional basis of the currently known CAH variants, with a specific focus on ORD.
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PMID:Congenital adrenal hyperplasia and P450 oxidoreductase deficiency. 1722 83

Congenital adrenal hyperplasia (CAH) is a group of inherited disorders caused by enzyme deficiencies in steroid biosynthesis, which disrupt the conversion of cholesterol to cortisol. The most common form of CAH is 21-hydroxylase deficiency (21-OHD). In its severe form, 21-OHD causes prenatal virilization of external female genitalia. Through molecular genetic analysis of fetal DNA, defects in 21-OH synthesis can be diagnosed in utero. Genital ambiguity in females can be reduced or eliminated with prenatal dexamethasone treatment, which successfully suppresses fetal androgen production. Data from current, large cohort studies show that prenatal diagnosis and treatment are safe and effective.
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PMID:Prenatal diagnosis and treatment of congenital adrenal hyperplasia. 1734 26

Classical forms of congenital adrenal hyperplasia are caused by a severe deficiency of 21-hydroxylase, an enzyme involved in steroid biosynthesis, which triggers excessive androgen production before birth. Affected females experience virilization both physically and psychologically. Prenatal diagnosis and treatment of congenital adrenal hyperplasia has been implemented for more than 20 years. In utero gene-specific diagnosis is now feasible for fetal cell samples derived from chorionic villi or amniotic cells in culture, and this gene-specific diagnosis guides the treatment of the affected female fetus. Appropriate dexamethasone administration to the at-risk pregnant mother is effective in reducing genital virilization in the fetus, and thus avoids unnecessary genitoplasty in affected females. Current data from large human studies show the benefit and safety of prenatal treatment. Long-term follow-up of the safety of prenatal treatment is currently underway. This practice is a rare example of effective prenatal treatment to prevent a malformation caused by an inborn error of metabolism.
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PMID:Prenatal diagnosis and treatment of congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. 1745 67

The phenotypes of the polycystic ovarian syndrome (PCOS) and congenital adrenal hyperplasia syndrome (CAHS) present a number of similarities. The main symptoms of PCOS are obesity, menstrual disorders, hirsutism, and low fertility in which the pituitary and adrenal glands are spared. The CAHS is a group of various entities all characterised by different degrees of malfunction of the 21-hydroxylase (CYP21) enzyme. The consequences are a downfall of the levels of aldosterone and cortisol, and the hyperproduction of adrenal androgen hormones. It is capital to be able to recognise these 2 entities in terms of identification of high risk families because the female foetuses suffering from CAHS will undergo severe virilization of there genitals in utero, which can efficiently be prevented by a administration of corticotherapy to the mother throughout the pregnancy.
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PMID:[Polycystic ovary syndrome and congenital adrenal hyperplasia: a different entity for comparable phenotypes?]. 1772 72

Congenital adrenal hyperplasia is a group of monogenic autosomal recessive disorders due to an enzyme deficiency in steroid biosynthesis. The most frequent form of congenital adrenal hyperplasia is 21-hydroxylase (21-OH) deficiency, which in its severe form can cause ambiguous genitalia in the female patient. Recent advances in molecular genetic analysis allow for prenatal diagnosis and treatment of at-risk fetuses. The objective of prenatal diagnosis and treatment of 21-OH deficiency is the prevention of prenatal virilization in affected female infants, reducing the risks of sex misassignment and gender confusion, and the need for corrective genital surgery. Prenatal treatment of 21-OH deficiency is effective in reducing genital ambiguity, and short-term outcome studies of children exposed to dexamethasone in utero indicate no significant adverse effects. However, more long-term studies of treated versus untreated pregnancies are warranted to monitor the safety of treatment and enhance our understanding of the effects of prenatal steroid exposure to the human brain. In the first year of life, optimization of medical treatment in salt-wasting patients is achieved by combining the lowest dose of glucocorticoid able to suppress androgen secretion with the normalization of sodium balance by giving appropriate sodium chloride supplementation.
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PMID:Prenatal and early postnatal treatment of congenital adrenal hyperplasia. 1798 27

46,XX individuals with classical congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme, 21-hydroxylase, show variable degrees of masculinization of body and behavior due to excess adrenal androgen production. Increased bisexuality and homosexuality have also been reported. This article provides a review of existing reports of the latter and presents a new study aimed at replicating the previous findings with detailed assessments of sexual orientation on relatively large samples, and at extending the investigation to the mildest form, non-classical (NC) CAH. Also, this is the first study to relate sexual orientation to the specific molecular genotypes of CAH. In the present study, 40 salt-wasters (SW), 21 SV (simple-virilizing), 82 NC, and 24 non-CAH control women (sisters and female cousins of CAH women) were blindly administered the Sexual Behavior Assessment Schedule (SEBAS-A, 1983 ed.; H. F. L. Meyer-Bahlburg & A. A. Ehrhardt, Privately printed). Most women were heterosexual, but the rates of bisexual and homosexual orientation were increased above controls not only in women with classical CAH, but also in NC women, and correlated with the degree of prenatal androgenization. Classifying women by molecular genotypes did not further increase the correlation. Diverse aspects of sexual orientation were highly intercorrelated, and principal components analysis yielded one general factor. Bisexual/homosexual orientation was (modestly) correlated with global measures of masculinization of non-sexual behavior and predicted independently by the degree of both prenatal androgenization and masculinization of childhood behavior. We conclude that the findings support a sexual-differentiation perspective involving prenatal androgens on the development of sexual orientation.
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PMID:Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. 1815 28

During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase are to prevent salt loss and virilization and to attain normal stature and normal puberty. As such, there is a narrow therapeutic window through which the intended results can be achieved. In adulthood, the clinical management has received little attention, but recent studies have shown the relevance of long-term follow-up of these patients. The aims here are to review the multiple clinical, hormonal and metabolic abnormalities that could be found in adult CAH patients as such a decrease in bone mineral density, overweight and disturbed reproductive functions. In women with classic CAH, a low fertility rate is reported, and is probably the consequence of multiple factors including neuroendocrine and hormonal factors, feminizing surgery, and psychological factors. Men with CAH may present hypogonadism either through the effect of adrenal rests or from suppression of gonadotropins resulting in infertility. Therefore a multidisciplinary team with knowledge of CAH should carefully follow up these patients, from childhood through to adulthood, to avoid these complications and to ensure treatment compliance and tight control of the adrenal androgens.
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PMID:Classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults. 1820 67

Females with salt-wasting (SW) 21-hydroxylase deficiency (21OHD) may present with mild external genitalia virilization, despite complete or almost complete enzyme inactivation. We therefore analyzed genotype/phenotype correlation in 13 Japanese female patients with SW 21OHD. Criteria for classification into the SW phenotype included history of a salt-losing crisis with documented hyponatremia, hyperkalemia, and markedly elevated plasma renin activity. Urologists and pediatricians determined the Prader genital stage and classified the location of the vaginal entrance into the common urogenital sinus as low, moderate, or high. CYP21A2 gene, coding for 21-hydroxylase, was analyzed with Southern blotting and direct sequencing. Genotypes were categorized into four mutation groups, based on the degree of enzymatic activity (N, complete enzyme inactivation; groups A, < 2%, B, 3-7%, and C > 30%). Basal androgen levels were available from only six out of thirteen patients, so we could not relate androgen levels with the severity of external genitalia virilization. We compared the degree of external genitalia virilization with genotype. The severity of external genitalia virilization varied from Prader stage 1 to 4. One patient who presented with Prader 1 had a genotype consistent with Group B. In addition, discordance between Prader classification and the location of the vaginal entrance was noted; one patient classified as Prader 4 showed low vaginal entrance, while another patient classified as Prader 3 showed high vaginal entrance. The degree of the impairment of 21-hydroxylase activity does not correlate with the severity of virilization of the external genitalia in female patients with the SW type of 21OHD.
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PMID:Severity of virilization of external genitalia in Japanese patients with salt-wasting 21-hydroxylase deficiency. 1867 8

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations.
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PMID:Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists. 1922 39

We provide evidence regarding the nature, causes, and consequences of intelligence in patients with 21-hydroxylase deficient congenital adrenal hyperplasia (CAH). Intelligence and quality of life (psychological adjustment) were measured on multiple occasions from childhood to young adulthood in 104 patients with CAH (62 females, 42 males) and 88 unaffected relatives (31 females, 57 males). Information on disease severity (CAH type, age at diagnosis, genital virilization for girls) and salt-wasting crises was obtained from medical records. There was no evidence of intellectual deficit in either female or male patients with CAH. Intelligence was not significantly associated with psychological adjustment or disease characteristics. CAH itself does not appear to increase risk for poor intellectual function. In a sample of patients with generally good disease control, intelligence is not related to adjustment problems, disease severity, or salt-wasting crises.
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PMID:Normal intelligence in female and male patients with congenital adrenal hyperplasia. 2097 63


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