Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Maria I. New
  • Publisher : Academic Press
  • Release Date : 2013-08-22
  • Genre: Science
  • Pages : 406
  • ISBN 10 : 9780123914675

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Genetic Steroid Disorders Excerpt :

This is a comprehensive book addressing steroid disorders from hormonal, genetic, psychological, and surgical perspectives. It is meant to educate adult and pediatric endocrinologists, clinical geneticists, genetic counselors, reproductive endocrinologists, neonatologists, urologists, and psychoendocrinologists. It will assist these specialists in the diagnosis and treatment of steroid disorders. The book is written for postgraduate and faculty-level physicians. The content consists of steroid disorders, genetic bases for the disorder and case presentations of each disorder. Provides a common language for professionals to discuss and diagnose genetic steroid disorders Includes the very latest details on genetic tests and diagnoses Offers a strong understanding of the molecular basis for the diseases and therefore correct diagnosis and treatment of steroid disorders Presents insight into which medications to use based on the genetic makeup of a patient Teaches the best strategies and most effective use of genetic information in the patient counseling setting

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Maria I. New
  • Publisher : Academic Press
  • Release Date : 2023-02-01
  • Genre: Science
  • Pages : 0
  • ISBN 10 : 9780128214251

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Genetic Steroid Disorders Excerpt :

Genetic Steroid Disorders, Second Edition targets adult and pediatric endocrinologists, clinical geneticists, genetic counselors, reproductive endocrinologists, neonatologists, urologists, and psychoendocrinologists. It is designed to assist these specialists in the diagnosis and treatment of steroid disorders. This revision includes a new chapter on "Gonadotropins, Obesity and Bone" and new research on non-invasive prenatal diagnosis with cell-free DNA. Chapters are thoroughly updated covering steroid disorders, the genetic bases for the disorder and case presentations, This definitive reference belongs in every medical library! Presents a comprehensive, translational look at all aspects of genetic steroid disorders in one reference work Provides a common language for endocrinologists, geneticists, molecular pathologists, and genetic counselors to discuss and diagnose genetic steroid disorders Saves clinicians and researchers time in quickly accessing the very latest details on genetic tests and diagnoses as opposed to searching through thousands of journal articles Highlights significant discoveries with clinical relevance, presenting insight into which medications to use based on the genetic makeup of a patient Teaches the best strategies and most effective use of genetic information in the patient counseling setting

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : David E. Reichman
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128073025

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Genetic Steroid Disorders Excerpt :

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 steroid enzyme deficiencies outlined.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Nicole Reisch
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128073049

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Genetic Steroid Disorders Excerpt :

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.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Christa E. Flück
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072851

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Genetic Steroid Disorders Excerpt :

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 activities of several steroid and drug metabolizing P450 proteins. Mutations in POR may have variable effects on different P450 partner proteins depending on the location of the mutation. The POR mutations that disrupt the binding of cofactors have a negative impact on all partner proteins, while mutations causing subtle structural changes may lead to altered interaction with partner proteins and the overall effect may be different for each partner.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : David W. Russell
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072899

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Genetic Steroid Disorders Excerpt :

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 phenotype and in many other androgen actions and led to the development of drugs for the treatment of prostatic disease.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Yves Morel
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072837

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Genetic Steroid Disorders Excerpt :

The transformation of Δ5-3β-hydroxysteroids into the corresponding Δ4-3-keto-steroids is an essential step for the biosynthesis of all classes of active steroids: progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. These steroid hormones play a crucial role in the differentiation, development, growth, and physiological function of most human tissues. The 3β-HSD deficiency (OMIM +201810), transmitted in an autosomic recessive disorder, is characterized by varying degrees of salt wasting; in genetic males, fetal testicular 3ß-HSD deficiency causes an undervirilized male genitalia (male pseudohermaphroditism); females exhibit either normal sexual differentiation or mild virilization.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Berenice B. Mendonca
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072882

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Genetic Steroid Disorders Excerpt :

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 inside the scrotum. The phenotype of 46,XY disorders of sex development (DSD) owing to 17β-HSD3 deficiency is extremely variable and is clinically indistinguishable from other causes of 46,XY DSD such as partial androgen insensitivity syndrome and 5α-reductase 2 deficiency. Laboratory diagnosis is based on elevated serum levels of androstenedione and estrone and low levels of testosterone and estradiol, resulting in elevated androstenedione:testosterone and estrone:estradiol ratios, indicating an impairment of the conversion of 17-keto into 17-hydroxysteroids. The disorder is due to homozygous or compound heterozygous mutations in the HSD17B3 gene that encodes the 17β-HSD3 isoenzyme. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. Our proposal in this article is to review the reported and our own cases of 17β-HSD3 deficiency.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Amrit Bhangoo
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128073070

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Genetic Steroid Disorders Excerpt :

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 Book

Genetic Steroid Disorders


  • Author : Hayk Barseghyan
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072950

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Genetic Steroid Disorders Excerpt :

Ovotesticular DSDs (OT-DSDs) are disorders of sex development in which both testicular and ovarian tissues are present in the same individual. We review the phenotypic variability of OT-DSDs, their sex chromosome constitution, and their molecular genetics, which remain for most patients, poorly understood.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Walter L. Miller
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072868

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Genetic Steroid Disorders Excerpt :

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 insufficiency and 46,XY disorders of sexual development (DSD). The lipoid CAH phenotype, including spontaneous puberty in 46,XX females, is explained by a two-hit model. StAR mutations that retain partial function cause milder non-classic disease characterized by glucocorticoid deficiency, with lesser disorders of mineralocorticoid and sex steroid synthesis. Rare P450scc mutations are clinically and hormonally indistinguishable from lipoid CAH, and may also present as milder non-classic disease. Adrenal imaging may distinguish these but is not 100% reliable, necessitating DNA sequencing.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Mabel Yau
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072929

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Genetic Steroid Disorders Excerpt :

Apparent mineralocorticoid excess (AME) is a rare inherited form of hypertension caused by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD) deficiency. The disorder was first described biochemically and hormonally in 1977 by New et al. in a Native American girl with severe hypertension. AME defined an important “pre-receptor” pathway in steroid hormone action and their specificities to the receptor. The exploration of the pathogenesis of AME opened a new area in receptor biology as a result of the demonstration that the specificity of the mineralocorticoid receptor function depends on a metabolic enzyme (11β-HSD2) rather than the receptor itself. The clinical manifestations of AME mimic those of excessive mineralocorticoid activity, but plasma levels of aldosterone and other known mineralocorticoids are not elevated. Affected patients may present with low birthweight, failure to thrive, severe hypertension, hypercalciuria and renal failure. The hypertension is severe, with onset in early childhood.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Anna Biason-Lauber
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072905

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Genetic Steroid Disorders Excerpt :

Following development of the fetal bipotential gonad into a testis, male genital differentiation requires testicular androgens. Fetal Leydig cells produce testosterone that is converted to dihydrotestosterone in genital skin, resulting in labioscrotal fusion. An alternative “backdoor” pathway of dihydrotestosterone synthesis that bypasses testosterone has been described in marsupials, but its relevance to human biology has been uncertain. The classic and backdoor pathways share many enzymes, but a 3α-reductase, AKR1C2, is unique to the backdoor pathway. Human AKR1C2 mutations cause disordered sexual differentiation, establishing that both pathways are required for normal human male genital development. These observations show that fetal dihydrotestosterone acts both hormonally and as a paracrine factor, substantially revising the classic paradigm for fetal male sexual development.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Perrin C. White
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072813

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Genetic Steroid Disorders Excerpt :

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 steroid 11β-hydroxylase deficiency, a form of congenital adrenal hyperplasia. Mutations in CYP11B2 result in aldosterone synthase deficiency, which can cause hyponatremia, hyperkalemia and hypovolemia in infancy. These are both recessive disorders. Unequal crossing over between the CYP11B genes can generate a duplicated chimeric gene, causing glucocorticoid-suppressible hyperaldosteronism, an autosomal dominant form of hypertension. Frequent polymorphisms in these genes can affect aldosterone secretion and risk of hypertension.

Genetic Steroid Disorders Book

Genetic Steroid Disorders


  • Author : Sowmya Krishnan
  • Publisher : Elsevier Inc. Chapters
  • Release Date : 2013-08-22
  • Genre: Medical
  • Pages : 406
  • ISBN 10 : 9780128072820

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Genetic Steroid Disorders Excerpt :

Ambiguous genitalia can be associated with disorders of sex development (DSD). DSD occurs when a person is born with discordant genetic, gonadal, or anatomic sex. Here we discuss typical-appearing external genital appearance in unaffected males and females followed by descriptions of ambiguous genitalia in newborns with 46,XY DSD, 46,XX DSD, syndromes associated with multiple congenital anomalies including, but not limited to, ambiguous genitalia, ovotesticular DSD, and mixed gonadal dysgenesis in newborns who possess a Y chromosome. We provide guidance to proceed with a clinical work-up to differentiation between types of DSD that result in ambiguous genitalia at birth. Finally, we discuss how gender assignments are made for newborns with DSD including ambiguous genitalia.