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 Genetic Steroid Disorders written by Maria I. New and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 63 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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 an accumulation of 17-hydroxyprogesterone (17-OHP) and subsequent elevation of androgens. The three forms of 21OHD are the salt-wasting form, simple-virilizing form, and non-classical form. The first two forms are classical forms of the disease where the hallmark finding is ambiguity of the genitalia in affected female newborns. Patients with the non-classical form have normal genitalia, yet may present with signs of early sexual development and other symptoms of hyperandrogenemia such as short stature, hirsutism, acne, and impaired fertility. Hormonal testing is important in making the diagnosis of 21-hydroxylase deficiency, yet genetic testing is crucial to secure the diagnosis. More than 100 mutations have been identified caused by gene conversions, large scale gene deletions, and de novo mutations, and novel mutations are continuously being identified. Genotype–phenotype non-concordance is observed in a significant number of patients.

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 Phyllis W. Speiser 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: 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 opinion and consensus of the endocrine community, as reflected in The Endocrine Society’s 2010 Clinical Practice Guidelines for the treatment of CAH (J Clin Endocrinol Metab 95: 4133–60).

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 Amrit Bhangoo and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 23 pages. Available in PDF, EPUB and Kindle. Book 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.

Download or read book Genetic Steroid Disorders written by Heino F.L. Meyer-Bahlburg and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 45 pages. Available in PDF, EPUB and Kindle. Book excerpt: The syndromes of congenital adrenal hyperplasia, particularly their classical variants, present diverse medical and psychosocial challenges to the affected individual that may affect all stages of life from the prenatal phase through old age. This chapter reviews the psychological outcomes in terms of gender, general cognitive development, psychopathology, sexuality, and quality of life, the factors that contribute to these outcomes, including neuroanatomy and brain function, and the implications for the clinician and the organization of health services.

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 Perrin C. White and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 43 pages. Available in PDF, EPUB and Kindle. Book 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.

Download or read book Genetic Steroid Disorders written by Richard C. Rink and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: Surgical treatment of congenital adrenal hyperplasia has undergone dramatic evolution over the past 30 years. This chapter will explore current reconstructive techniques and historic as well as current surgical outcomes. A brief description of surgical technique and its evolution will be described, followed by an analysis of surgical outcomes. The chapter will conclude with a discussion regarding current controversies regarding timing and technique of surgical correction.

Download or read book Genetic Steroid Disorders written by Denesy Mancenido and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 31 pages. Available in PDF, EPUB and Kindle. Book excerpt: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroidogenesis, which causes virilization of external genitalia in females affected with the severe form of the disease. However, genital ambiguity is preventable with prenatal treatment with dexamethasone during the first trimester. While prenatal treatment has remained largely unchanged since its institution, prenatal diagnosis of CAH has witnessed a number of advancements in the past 50 years. The first successful prenatal diagnosis utilized hormonal measurements of the amniotic fluid. Elevated levels of 17α-hydroxyprogesterone in the amniotic fluid became diagnostic for a fetus affected with the severe form of the disorder. This finding was followed by the discovery of the close linkage between the disease and the HLA complex, which led to HLA linkage studies as a second approach for prenatal diagnosis. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the third method for prenatal diagnosis. Using polymerase chain reaction (PCR)-based methods to amplify the CYP21A2 active gene, and not the CYP21A1P pseudogene, diagnostic procedures increased in specificity and led to accurate prenatal diagnosis in the first trimester. The advent of non-invasive prenatal diagnosis heralds a new development for prenatal diagnosis of CAH, with the potential for improved safety, earlier detection, and increased accessibility.

Download or read book Genetic Steroid Disorders written by Felix Beuschlein 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: Adrenal disorders that are caused by specific genetic alterations comprise a heterogeneous group of diseases with mostly low incidence that can affect patients from birth to adulthood. These conditions include failure of proper adrenal development resulting in adrenal agenesis or, conversely, adrenal tumorigenesis. Furthermore, deficiencies of adrenal steroidogenesis result in a lack or a shift of adrenal steroid production that can cause a specific clinical phenotype. For functional studies of gene products, mouse models remain to be intensively utilized as an experimental system owing to the similarity to humans with respect to genome organization, development, and physiology. For the majority of adrenal genetic disorders, mouse models exist that in most instances resemble the clinical phenotype observed in affected patients. Here we provide an overview of these models that allows for both mechanistic and therapeutically relevant investigations that will eventually translate into improved patient care.

Download or read book Genetic Steroid Disorders written by Charles Sultan and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 39 pages. Available in PDF, EPUB and Kindle. Book excerpt: After reviewing the mechanisms of androgen action, we will look at the main clinical features of androgen insensitivity, as well as the biological, cellular, and molecular tools used to investigate the AR. Numerous AR mutations have been described over the past 20 years. We will consider the challenges for diagnosis and prognosis by examining the genotype–phenotype relationship and the possibility of somatic mutations. Last, we will address the role of genetic counseling and the elements that should be taken into account for the difficult decision of sex assignment in children affected with AIS.

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 Genetic Steroid Disorders written by John W. Funder and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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 to be prompt, vigorous, and appropriate in terms of rectifying electrolyte abnormalities and lowering blood pressure.

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 Yewei Xing and published by Elsevier Inc. Chapters. This book was released on 2013-08-22 with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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 trophic hormones controlled by the hypothalamus–pituitary endocrine axes. Adrenal organogenesis and development of adult steroidogenesis are carefully orchestrated by action of a number of gene products. Although the pattern of development differs somewhat in diverse primates, the same genes appear to regulate the basic developmental program in all mammalian species. Most basic laboratory research is done in mice, in which prenatal development occurs within a compressed period of approximately 19 days and in which adrenals at birth are considerably less developed than in their human counterparts. This chapter describes the contributions of genes responsible for the proper development of the adrenal cortex, as well as how an understanding of adrenal gland disease provides novel fundamental insights into the regulation of adrenal development and steroidogenesis.