Genetic Steroid Disorders

Over the past two decades, genetics of congenital adrenal hyperplasia (CAH) have been extensively studied. The introduction of newborn screening programs in most western countries for CAH caused by 21-hydroxylase deficiency (21OHD) and genetic studies in different ethnic populations have enabled more accurate data concerning the distribution and incidence of CAH and revealed ethnic-specific mutations. Worldwide, the most common mutations in the severe salt-wasting form of 21OHD are the IVS2, the intron 2 splicing mutation, and a large deletion in exon 3. In non-classic 21OHD the most common mutation worldwide is V281L (1685 G to T), being prevalent in about 60% of non-classic patients. This article summarizes the current knowledge on the observed geographical differences of mutation spectra of CAH in specific ethnic groups.

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  • Author : Nicole Reisch
  • Publisher : Elsevier Inc. Chapters
  • Pages : 406 pages
  • ISBN : 0128073047
  • Rating : 4/5 from 21 reviews
CLICK HERE TO GET THIS BOOKGenetic Steroid Disorders

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Nicole Reisch,Ursula Kuhnle
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

Over the past two decades, genetics of congenital adrenal hyperplasia (CAH) have been extensively studied. The introduction of newborn screening programs in most western countries for CAH caused by 21-hydroxylase deficiency (21OHD) and genetic studies in different ethnic populations have enabled more accurate data concerning the distribution and incidence of CAH and revealed ethnic-specific mutations. Worldwide, the most common mutations in the severe salt-wasting form of 21OHD are the IVS2, the intron 2 splicing mutation, and a large deletion in exon 3.

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Maria I. New
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

This book demonstrates that each steroid disorder causing both clinical and biochemical abnormalities in patients now has a genetic basis. The genes for each step in steroidogenesis have been mapped and cloned, and the mutations in the gene causing the disorder have been described. In addition, the structural biology of the protein resulting from the mutation in the gene has been reported for many of the disorders.

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Christa E. Flück,Amit V. Pandey
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
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Cytochrome P450 oxidoreductase (POR) is an enzyme that is essential for multiple metabolic processes; chiefly among them are reactions catalyzed by cytochrome P450 proteins for metabolism of steroid hormones, drugs, and xenobiotics. Mutations in POR cause a complex set of disorders that often resemble defects in steroid metabolizing enzymes 17-hydroxylase, 21-hydroxylase, and aromatase. Since the initial reports of POR mutations in 2004, more than 70 different mutations and polymorphisms in the POR gene have been identified and tested for their effect on

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Richard J. Auchus
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
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Steroid 17-hydroxylase 17,20-lyase (cytochrome P450c17, CYP17A1) occupies a critical position in the pathways of human steroidogenesis, regulating the classes of steroid hormones produced by cells of the adrenal glands and gonads. CYP17A1 catalyzes two major reactions: the 17-hydroxylase and 17,20-lyase reactions. Mutations that compromise all CYP17A1 activities cause combined 17-hydroxylase/17,20-lyase deficiency, which presents as hypertension, hypokalemia, and sexual infantilism. A few mutations selectively impair 17,20-lyase activity, and some mutations in cofactor proteins cytochrome P450-oxidoreductase

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Phyllis W. Speiser
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
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Congenital adrenal hyperplasia (CAH) is among the group of inherited disorders now included in newborn screening programs throughout the USA and in many other developed countries. As patients are diagnosed earlier and survive longer into adult life, current therapeutic dilemmas concern individual quality of life, adherence to ethical principles of medical practice, and cost–benefit analysis. This paper will discuss current thinking on selected controversies in the medical and surgical management of CAH. This discussion is based mainly on expert

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Maria I. New,Oksana Lekarev,Denesy Mancenido,Alan Parsa,Tony Yuen
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive genetic disorders that arise from defective steroidogenesis. The 21-hydroxylase deficiency (21OHD) is the most common form of CAH, accounting for more than 90% of cases. It is the most common disorder of sexual development (DSD) in females. The gene is encoded by CYP21A2, which is located on the short arm of chromosome 6 (6p21.3). The activity of the enzyme 21-hydroxylase, encoded by the CYP21A2 gene, is deficient, leading to

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : David E. Reichman,Zev Rosenwaks
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
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Human genetic steroid defects have profound impacts on the reproductive potential of affected individuals. Fortunately, advances in our understanding of the genetic and physiologic nuances of these disorders have led to the successful restoration of fertility for patients with several such diseases. In this chapter, the genetic steroid disorders will be explored with respect to their effects on human reproduction, the mechanisms whereby fertility is limited or precluded will be described, and existing as well as emerging therapies for genetic

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Walter L. Miller,Zoran S. Gucev
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
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Steroidogenesis begins with internalization of low-density lipoprotein particles and subsequent intracellular processing of cholesterol. Disorders in these steps include adrenoleukodystrophy, Wolman disease, and Niemann–Pick type C disease, which may present as adrenal insufficiency. Cholesterol delivery to the inner mitochondrial membrane is regulated by the steroidogenic acute regulatory protein, StAR, and cholesterol is converted to pregnenolone within mitochondria by the cholesterol side chain cleavage enzyme, P450scc. Severe StAR mutations cause classic congenital lipoid adrenal hyperplasia (CAH), characterized by adrenal

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Yewei Xing,John C. Achermann,Gary D. Hammer
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
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The adrenal glands comprise two distinct endocrine organs: the inner medulla and the outer cortex. The inner medulla is made up of neuroectodermal cells derived from the neural crest and produces the catecholamine hormones norepinephrine and epinephrine, which are crucial for stress responses. The outer cortex is derived from the mesoderm and synthesizes steroid hormones that are essential to maintain fluid and electrolyte balance, modulate intermediary metabolism and regulate inflammatory processes. Steroidogenesis in the adrenal cortex is mainly regulated by

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Perrin C. White
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

Humans have two isozymes with 11β-hydroxylase activity that are respectively required for cortisol and aldosterone synthesis. CYP11B1 (11β-hydroxylase) converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone, is expressed at high levels and is regulated by ACTH. CYP11B2 (aldosterone synthase) is normally expressed at low levels and is regulated mainly by angiotensin II and potassium levels. The latter enzyme also has 18-hydroxylase and 18-oxidase activities and thus can synthesize aldosterone from deoxycorticosterone. Mutations in the CYP11B1 gene cause

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : John W. Funder
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

Apparent mineralocorticoid excess (AME) reflects absent or impaired activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2, allowing cortisol to activate epithelial mineralocorticoid receptors inappropriately. In the absence of enzyme activity patients show classic features of mineralocorticoid excess, with a diagnostic triad of hypertension, suppressed aldosterone levels, and raised urinary free cortisol:cortisone ratios. Severe AME (10%) can be diagnosed on the basis of the diagnostic triad, but do not show the associated spectrum of clinical disorders. Treatment of severely affected neonates needs

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Amrit Bhangoo,Svetlana Ten
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

A 46,XY DSD is a condition in which a child has a 46,XY genotype but in whom gonadal, or anatomical, sex is atypical. A 46,XY DSD can be caused by multiple etiologies, most commonly involving disruption in both androgen production and/or action.

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Berenice B. Mendonca,Elaine M.F. Costa,Marlene Inacio,Ari A. Oliveira Junior,Regina M. Martin,Mirian Y. Nishi,Aline Z. Machado,Filomena Marino Carvalho,Francisco Denes Tibor,Sorahia Domenice
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

17β-hydroxysteroid dehydrogenase 3 deficiency (17β-HSD3) consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. Patients present female-like or with ambiguous genitalia at birth and most affected males are raised as females. Virilization in subjects with 17β-HSD3 deficiency occurs at the time of puberty and almost half change to be males. Maintenance of the testes in patients raised male is safe and recommended, except when the testes cannot be positioned

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : Nathalie Josso,Richard L. Cate,Jean-Yves Picard
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

The persistent Müllerian duct syndrome (PMDS) is characterized by the persistence of Müllerian derivatives in otherwise normally virilized XY individuals. The condition is usually due to a mutation in either the anti-Müllerian hormone (AMH) or the AMH type II receptor (AMHR-II) genes and is transmitted as a recessive autosomal trait. Sixty-five families with AMH mutations and 59 with AMHR-II mutations have been reported to date. Clinical symptoms include cryptorchidism and/or inguinal hernia, and are identical for ligand

Genetic Steroid Disorders

Genetic Steroid Disorders
  • Author : David W. Russell,Jean D. Wilson
  • Publisher : Elsevier Inc. Chapters
  • Release : 22 August 2013
GET THIS BOOKGenetic Steroid Disorders

Loss-of-function mutations in the steroid 5α-reductase 2 gene (SRD5A2) cause a disorder of male sexual differentiation in which the prostate does not form and external genitalia develop along female lines. Failure to synthesize dihydrotestosterone in fetal tissues that give rise to the male urogenital tract underlies the phenotype that characterizes this disorder. Studies of the SRD5A2 gene and its encoded enzyme at the molecular, biochemical, and endocrinological levels established the crucial role of dihydrotestosterone in formation of the male