Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Maria I. New

Publisher: Academic Press

Published: 2023-06-14

Total Pages: 470

ISBN-13: 0128214252

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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


Book Synopsis Genetic Steroid Disorders by : Maria I. New

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

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Maria I. New

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 63

ISBN-13: 0128072784

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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.


Book Synopsis Genetic Steroid Disorders by : Maria I. New

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Nicole Reisch

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 22

ISBN-13: 0128073047

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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.


Book Synopsis Genetic Steroid Disorders by : Nicole Reisch

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Phyllis W. Speiser

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 25

ISBN-13: 0128073055

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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 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).


Book Synopsis Genetic Steroid Disorders by : Phyllis W. Speiser

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).

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Amrit Bhangoo

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 23

ISBN-13: 0128073071

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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.


Book Synopsis Genetic Steroid Disorders by : Amrit Bhangoo

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Walter L. Miller

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 58

ISBN-13: 0128072865

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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 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.


Book Synopsis Genetic Steroid Disorders by : Walter L. Miller

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Heino F.L. Meyer-Bahlburg

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 45

ISBN-13: 0128072989

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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.


Book Synopsis Genetic Steroid Disorders by : Heino F.L. Meyer-Bahlburg

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Perrin C. White

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 43

ISBN-13: 0128072814

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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.


Book Synopsis Genetic Steroid Disorders by : Perrin C. White

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: Felix Beuschlein

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 22

ISBN-13: 0128073012

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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.


Book Synopsis Genetic Steroid Disorders by : Felix Beuschlein

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.

Genetic Steroid Disorders

Genetic Steroid Disorders

Author: David E. Reichman

Publisher: Elsevier Inc. Chapters

Published: 2013-08-22

Total Pages: 37

ISBN-13: 0128073020

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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 steroid enzyme deficiencies outlined.


Book Synopsis Genetic Steroid Disorders by : David E. Reichman

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.