Download or read book Genetic Steroid Disorders written by Maria I. New and published by Academic Press. This book was released on 2023-06-14 with total page 470 pages. Available in PDF, EPUB and Kindle. Book 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
Download or read book Podocytopathy written by Z.-H. Liui and published by Karger Medical and Scientific Publishers. This book was released on 2014-05-16 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: The podocyte is a key cell that forms the last barrier of the kidney filtration unit. One of the most exciting developments in the field of nephrology in the last decade has been the elucidation of its biology and its role in the pathophysiology of inherited and acquired glomerular disease, termed podocytopathy. In this publication, world-renowned experts summarize the most recent findings and advances in the field: they describe the unique biological features and injury mechanisms of the podocyte, novel techniques used in their study, and diagnosis and potential therapeutic approaches to glomerular diseases. Due to its broad scope, this publication is of great value not only for clinical nephrologists and researchers, but also for students, residents, fellows, and postdocs.
Download or read book Genetic Steroid Disorders written by Berenice B. Mendonca and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 25 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by David E. Reichman and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 37 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Christa E. Flück and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 56 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by David W. Russell and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 44 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Nicole Reisch and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 22 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Anna Biason-Lauber and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 34 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Walter L. Miller and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 58 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Yves Morel and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 35 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by David M. Lonard and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 37 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nuclear receptors are transcription factors that bind steroid, retinoid and thyroid hormones, and other ligands to drive hormone-dependent gene expression in conjunction with co-activators and co-repressors, collectively referred to as co-regulators. So far, more than 400 co-regulators have been reported in the literature and they have been implicated in a wide variety of pathological conditions, genetic syndromes, and in cancer. A key feature of co-regulator-based disease is the pleiotropic effects that disruption of normal co-regulator function has on energy metabolism, neurological function, and susceptibility to cancer. Technological advances in proteomics, genomics, and transcriptomics are leading to new ways to understand the pleiotropic actions of co-regulators. We expect that co-regulator ‘omics’ will lead to ways of understanding how co-regulators can be evaluated in the context of other complex genetic factors, hormones, diet, the environment, and stress. The broad role that co-regulators have in human pathological conditions makes it important to consider them as important new drug targets, such as for the treatment of hormone-dependent cancers or for indications related to energy metabolism. Better system-wide knowledge of co-regulator control of transcription and physiology is expected to lead to the best placement for future co-regulator-based therapies.
Download or read book Diagnosis and Management of Ovarian Disorders written by Albert Altchek and published by Elsevier. This book was released on 2003-09-04 with total page 595 pages. Available in PDF, EPUB and Kindle. Book excerpt: This updated second edition of Diagnosis and Management of Ovarian Disorders provides thorough, yet succinct insight into the ever-changing realm of ovarian disorders. It presents a novel multidisciplinary approach to the subject as described by clinicians, surgeons, pathologists, basic scientists and related medical researchers. Topics covered include reproductive technology, early diagnosis of ovarian cancer, and management of menopause among others. The breadth of information provided by this book will appeal to clinicians and researchers involved in the study and treatment of ovarian disorders.KEY FEATURES* Includes updated information on early diagnosis of ovarian cancer* Reviews new diagnostic techniques for ovarian disorders* Discusses latest information on reproductive technology* Presents translational treatment linking laboratory research with clinical medicine
Download or read book Genetic Steroid Disorders written by Mabel Yau and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 25 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Richard J. Auchus and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 36 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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 and cytochrome b5 also selectively disrupt 17,20-lyase activity. This chapter reviews the genetics, clinical presentation, management, and history of these disorders.
Download or read book Genetic Steroid Disorders written by Sowmya Krishnan and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 33 pages. Available in PDF, EPUB and Kindle. Book 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.
Download or read book Genetic Steroid Disorders written by Florencia Halperin and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 29 pages. Available in PDF, EPUB and Kindle. Book excerpt: Glucocorticoid-remediable aldosteronism (GRA) is a heritable form of primary hyperaldosteronism. As a result of a chimeric gene duplication, aldosterone synthase is expressed in the cortisol-producing zona fasciculata of the adrenal cortex and is regulated by adrenocorticotropin (ACTH). Clinically, GRA is characterized by early onset of hypertension, which may be severe and refractory to standard therapies. In the absence of treatment with diuretics, hypokalemia is uncommon. GRA is associated with a high prevalence of intracranial aneurysms and hemorrhagic stroke. Diagnostic testing for the presence of the chimeric gene is available. The mainstay of treatment is glucocorticoid suppression of ACTH, and alternatives include mineralocorticoid receptor antagonism.
Download or read book Genetic Steroid Disorders written by Jonathan F. Russell and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 80 pages. Available in PDF, EPUB and Kindle. Book excerpt: Aromatase is a cytochrome P450 enzyme that catalyzes a critical step in the conversion of androgens (C19 steroids) to estrogens (C18 steroids). Mutations in the aromatase gene (CYP19A1) can result in a lack of aromatase activity and, as a consequence, impairment in estrogen biosynthesis. The functional consequences of this deficiency begin in utero owing to the inability of the placenta to convert androgens to estrogens. This disorder is termed aromatase deficiency (AD). Upon the initial identification of patients with AD, certain clinical findings, such as virilization of the pregnant mother and 46,XX fetus, were easily understood based on the known effects of placental aromatase on the conversion of C19 androgens and androgen precursors to estrogens. However, the discovery that the lack of estrogens in both females and males with AD leads to the absence of a pubertal growth spurt, delayed bone age, delayed epiphyseal fusion, and decreased accrual of bone mass in the male (not only in the female) has transformed our understanding of the role of estrogen on the male skeleton. It is now established that in both females and males, estrogen induces the pubertal growth spurt and mediates epiphyseal fusion. In this chapter we summarize the clinical characteristics, pathophysiology, differential diagnosis, and treatment of human AD. The implications of AD for the clinical use of aromatase inhibitors are reviewed.
