Genetic Steroid Disorders
- 1st Edition - September 24, 2013
- Language: English
This is a comprehensive book addressing steroid disorders from hormonal, genetic, psychological, and surgical perspectives. It is meant to educate adult and pediatric en… Read more
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
Adult and pediatric endocrinologists, academic and clinical researchers in endocrinology and clinical genetics, geneticists, genetic counselors, and psychoendocrinologists.
Dedication
Preface
Contributors
Chapter 1. Introduction
Abstract
References
Chapter 2. Adrenal Development
Abstract
Introduction
Adrenal Organogenesis
Molecular Mechanisms That Regulate Adrenal Development
Adrenal Diseases
References
Chapter 3A. Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency
Abstract
Introduction
Endocrine Function of the Adrenal Cortex
The Adrenal Cortex as Two Glands
Pathogenesis of 21-Hydroxylase Deficiency
Classical CAH
Non-Classical CAH
Diagnosis (Hormonal and Genetic)
Molecular Mechanisms Creating Cyp21a2 Genetic Defects
Clinical Features
Treatment
Prenatal Diagnosis and Treatment
References
Chapter 3B. The History of Prenatal Diagnosis of Congenital Adrenal Hyperplasia
Abstract
Introduction
Hormonal Measurements in Amniotic Fluid
Molecular Genetics
Dexamethasone Treatment and Controversy
Non-Invasive Prenatal Diagnosis
Fetal Sex Determination
Future Directions
Summary
References
Chapter 3C. Growth Hormone Therapy to Improve Adult Height in Patients with Congenital Adrenal Hyperplasia
Abstract
Introduction
Adult Height in CAH
Factors Affecting Adult Height in CAH
Studies with Growth Hormone Treatment to Improve Adult Height in CAH
Conclusion
References
Chapter 3D. Steroid 11β-Hydroxylase Deficiency and Related Disorders
Abstract
Acknowledgments
Introduction
Biochemistry of Adrenal Steroid Biosynthesis
Genetics of Steroid 11β-Hydroxylase Isozymes
Steroid 11β-Hydroxylase Deficiency
Aldosterone Synthase (Corticosterone Methyloxidase) Deficiency
Glucocorticoid-Suppressible Hyperaldosteronism
References
Chapter 3E. Ambiguous Genitalia in Newborns
Abstract
Introduction
Typical Sex Determination and Differentiation
Disorders of Sex Development (DSD)
Other Categories of Ambiguous Genitalia
Work-Up of Newborns with Ambiguous Genitalia
Differential Diagnosis
Gender of Rearing
Parents and Caregivers of Children with Ambiguous Genitalia
Conclusions
References
Chapter 3F. 3β-Hydroxysteroid Dehydrogenase Deficiency
Abstract
The 3β-HSD Family: Amino Acid Sequences and Activities
Epidemiology
Clinical Forms
Biological Diagnosis
Molecular Diagnosis
Relationship between Genotype and Phenotype of Patients
Puberty and Fertility
Structure–Function Relationship
Treatment
References
Chapter 3G. Genetic Deficiencies of Cytochrome P450c17 (CYP17A1): Combined 17-Hydroxylase/17,20-Lyase Deficiency and Isolated 17,20-Lyase Deficiency
Abstract
Structure of the Gene and Mapping in the Human Genome
Genetic Defects – Mutation
Hormonal Abnormalities
Diagnosis Based on Structure of the Gene and Mutations
Epidemiology
Ethnic Diversity and Clusters of the Defect
Psychoendocrine Abnormalities Resulting from the Enzymatic Defect
Treatment: Medical and Surgical
Long-Range Outcome: Medical and Psychological (Gender, Cognition)
Life Careers
Prismatic Cases
Prenatal Diagnosis and Treatment
References
Chapter 3H. P450 Oxidoreductase Deficiency (PORD)
Abstract
Acknowledgments
Introduction
The Biological Function of POR
Clinical Spectrum of PORD
The Steroid Metabolom of PORD and Diagnostic Pitfalls
POR Structure to Steroid Function Correlations
PORD and Skeletal Malformations
POR and Drug Metabolism
Heme Oxygenase
Cytochrome b5 and Small Molecules
POR Variants in the Human Population
Regulation of POR Gene Expression
Conclusions and Perspectives
References
Chapter 3I. Disorders in the Initial Steps in Steroidogenesis
Abstract
Intracellular Cholesterol Trafficking
Disorders of Intracellular Cholesterol Trafficking
Mitochondrial Cholesterol Import and the Acute Regulation of Steroidogenesis
References
Chapter 3J. Aromatase Deficiency and Aromatase Excess
Abstract
Acknowledgments
Introduction
Case Reports
Clinical Characteristics
Genetics
Pathophysiology
Differential Diagnosis
Treatment
Aromatase Inhibitors
Aromatase Excess Syndrome
Conclusion
References
Chapter 3K. 46,XY DSD due to 17β-Hydroxysteroid Dehydrogenase 3 Deficiency
Abstract
Acknowledgments
Introduction
Clinical Aspects
Gender Role
Biochemical Diagnosis
Histological Aspects
Molecular Findings
References
Chapter 4A. Steroid 5α-Reductase 2 Deficiency
Abstract
Introduction
The Enzymatic Reaction
Role of Dihydrotestosterone in Androgen Physiology
Why Dihydrotestosterone?
Role of Dihydrotestosterone in Male Sexual Development
Steroid 5α-Reductase 2 Deficiency
Diagnosis
Molecular Genetics
Management
Summary
References
Chapter 4B. Marsupial Pathway in Humans
Abstract
Acknowledgments
Role of Androgens in Fetal Male Differentiation
Sexual Development and Sexual Differentiation
The “Classic” Pathway of Androgen Biosynthesis
The Alternative “Backdoor” Pathway of Androgen Synthesis
Aldo Keto Reductases (AKR) and Steroidogenesis
Significance for Sexual Development
AKR1C2 Mutations Show that the Backdoor Pathway is Essential in Humans
Activities of the AKR1C2 Mutants
An Unrelated Individual Confirms the Key Role of AKR1C2
Modeling Studies
Sites of DHT Synthesis
Conclusions
References
Chapter 5. Androgen Insensitivity Syndrome
Abstract
Introduction
Androgen Action: Structure and Function of The AR
Clinical Features of AIS
Diagnosis of AIS
Phenotype–Genotype Correlations of AR Mutations
Management of AIS
Sex of Rearing
Conclusion
References
Chapter 6A. Apparent Mineralocorticoid Excess
Abstract
Background
Molecular Genetics
Clinical Presentation and Diagnosis
Treatment
Summary
References
Chapter 6B. The History, Biology, and Pathophysiology of Apparent Mineralocorticoid Excess
Abstract
Acknowledgments
References
Chapter 6C. Glucocorticoid-Remediable Aldosteronism
Abstract
Introduction
Pathophysiology and Genetic Basis of GRA
Epidemiology
Clinical Presentation
Biochemical Features
Other Forms of Familial Hyperaldosteronism
Diagnostic Approach
Treatment
Conclusion
References
Chapter 7. The Genetics of Ovotesticular Disorders of Sex Development
Abstract
Introduction
Phenotypic Features of OT-DSD
Genotypes of OT-DSD
Animal Models
Conclusion
References
Chapter 8. The Persistent Müllerian Duct Syndrome
Abstract
Introduction
AMH and The Müllerian DUCT: The Basics
The Patient with PMDS
Biology
Differential Diagnosis
AMH Gene Mutations
AMH Receptor Mutations
Idiopathic and Non-Characterized PMDS
References
Chapter 9. Treatment and Outcome of Congenital Adrenal Hyperplasia: Current Reconstructive Surgery
Abstract
Preoperative Evaluation
Endoscopy
Surgical Technique
Outcomes
References
Chapter 10. Psychoendocrinology of Congenital Adrenal Hyperplasia
Abstract
Introduction
Gender
General Cognitive Development
Psychiatric Outcome
Sexuality
Quality of Life
Implications for the Organization of Health Services for CAH
References
Chapter 11. Nuclear Receptor Co-regulators
Abstract
Introduction
Molecular Features of Co-Activators
Co-Activators Exist in Multiprotein Complexes
Co-Activators are Master Regulators of Gene Expression Programs
The Relationship Between Co-Regulators and Human Genetic Disorders
Co-Repressors and Genetic Disease
Co-Regulators and Cancer
Co-Activators and Resistance to Chemotherapy
Co-Activators as Drug Targets
Co-Regulator ‘Omics’: Using High-Throughput Data to Connect Co-Regulator Biology to Human Disease
Co-Activators, Our Environment and Human Evolutionary History
Co-Activators as Weakly Penetrant Disease Risk Alleles
Conclusions
References
Chapter 12. Genetics of Adrenal Tumors
Abstract
Genetics of Adrenocortical Tumors
Genetic Syndromes
Genes Frequently Dysregulated in Sporadic ACCs
Multistep Model of Adrenocortical Tumorigenesis – Evidence from Clinical Observations, Molecular Studies, and Animal Models
Histology does not Tell Everything – Genome-Wide Expression Profiles
Conclusion
References
Chapter 13A. Animal Models of Adrenal Genetic Disorders
Abstract
Introduction
Mouse Models for Congenital Adrenal Hypoplasia
Mouse Models for Familial Glucocorticoid Deficiency (ACTH Resistance Syndromes)
Mouse Models for Congenital Adrenal Hyperplasia
Mouse Models of Congenital Lipoid Adrenal Hyperplasia
Genetically Modified Mouse Models Displaying an Adrenal Tumor Phenotype
Mouse Models with Targeted Deletions Inducing Adrenal Tumors
References
Chapter 13B. The Impact of Genetic Steroid Disorders on Human Fertility
Abstract
Introduction
Adrenal Steroid Enzyme Deficiencies
Steroidogenic Acute Regulatory Protein (STAR)
Gonadal Steroid Enzyme Defects
Conclusion
References
Chapter 13C. Preimplantation Diagnosis and Other Modern Methods for Prenatal Diagnosis
Abstract
Introduction and Overview
Treatment
Expanding the Diagnostic Range in Prenatal Genetic Diagnosis by CGH in Chromosomal Microarrays (Array CGH)
Preimplantation Genetic Diagnosis
Changing Approaches in Prenatal Detection of Mendelian Disorders: Cell-Free Fetal DNA
Cell-Free Fetal DNA in Maternal Blood to Determine Gender
Cell-Free Fetal DNA in Maternal Blood to Detect Mendelian Disorders Showing Qualitative Maternal–Fetal Differences
Cell-Free Fetal DNA in Maternal Blood for Detection of CAH (21-Hydroxylase Deficiency)
Intact Fetal Cells in Maternal Blood: Earlier Detection of Fetal Mendelian Disorders?
Conclusion
References
Chapter 13D. Geographical Endocrinology of Genetic Steroid Disorders
Abstract
Introduction
Epidemiology – Screening Data
Genetic Studies in Various Ethnic Groups
Lessons Learned from “Consanguineous Populations”
Carrier Frequency of CAH in the General Population
Heterozygote Advantage in CAH Caused by 21OHD
Summary
References
Chapter 13E. Debates and Controversies in Genetic Steroid Disorders
Abstract
Controversy No.1: Prenatal Treatment of Virilizing Congenital Adrenal Hyperplasia
Controversy No.2: Genital Surgery
Controversy No.3: Growth Enhancement
References
Chapter 13F. Genetic Factors in Cushing Disease Pathogenesis
Abstract
Introduction
Pituitary Corticotroph Tumors
Animal Models
References
Chapter 13G. Case Reports of Unsolved Mysteries of Steroid Disorders: 46,XY DSD with One Clue
Abstract
Introduction
46,XY Dsd with Low Simulated T/Δ4 Ratio
Leydig Cell Hypoplasia in Two Siblings with 46,XY DSD
References
Index
Color Plates
"Appropriate for both novice and experienced researchers, this collection demonstrates that the genetic basis has been located for each steroid disorder causing clinical and bioclinical abnormalities in patients. Ten of the 31 chapters describe the symptoms, cause, diagnosis, and treatment of the many disorders resulting from congenital adrenal hyperplasia…the definitive treatise belongs in every medical library."—ProtoView.com, February 2014
"Appropriate for both novice and experienced researchers, this collection demonstrates that the genetic basis has been located for each steroid disorder causing clinical and bioclinical abnormalities in patients…Edited by a professor of pediatric endocrinology at Mount Sinai Hospital, the definitive treatise belongs in every medical library."—Reference & Research Book News, December 2013
- Edition: 1
- Published: September 24, 2013
- Language: English