Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Seventh Edition

Volume 1

7th Edition, Volume 1 - September 27, 2024
Imprint: Academic Press
Editors: Roger N. Rosenberg, Juan M. Pascual
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 0 4 1 - 4
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 0 4 2 - 1

Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Seventh Edition, provides a comprehensive introduction and reference to the foundations and key pr… Read more

Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Seventh Edition

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Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Seventh Edition, provides a comprehensive introduction and reference to the foundations and key practical aspects relevant to neurologic and psychiatric disease. This volume has been thoroughly revised and includes newly commissioned chapters on ethics, genetic counselling and genet therapy for the central nervous system disorders. A favorite of over four generations of students, clinicians and scholars, this new edition retains and expands the informative, concise and critical tone of the previous edition. This is an essential reference for general medical practitioners, neurologists, psychiatrists, geneticists, and related professionals, and for the neuroscience and neurology research community at large.

Title of Book
Cover image
Title page
Table of Contents
Copyright
The editors
Dedication
List of Contributors
About the editors
Foreword for the sixth edition
Prologue for the sixth edition
Introduction to the seventh edition
Section I: General concepts and tools
Chapter 1. Mendelian, non-Mendelian, multigenic inheritance, and epigenetics
Abstract
Introduction
Mendelian traits
Repeat expansion disorders
Non-Mendelian inheritance
Chromosomal and genomic disorders
Multigenic inheritance
Complex traits
Epigenetics
Assessing variation in the human genome
Next-generation sequencing
Conclusion
References
Chapter 2. Precision medicine in neurology
Abstract
Introduction
Technologies contributing to precision medicine
Metabolomics
Imaging
Wearable devices
Early precision medicine advancements
Initiation of precision medicine programs in the United States
Precision medicine results at individualized level (N-of-1)
Pharmacogenomics
Incorporation of precision diagnostics with targeted therapy
Summary
Acknowledgments
References
Chapter 3. Epigenomics of neurological disorders
Abstract
Introduction
Types and mechanisms of epigenetic modifications
Epigenetic therapeutic strategies in neurological disorders
Conclusions
References
Chapter 4. What genes can and cannot do
Abstract
Conceptual confusions in neurology and genetics
Genes are malleable
Biological causation: from and to genes and on to more important levels
What biological level(s) control the organism?
The crooked paths between genes and phenotypes
Abnormalities leading to normality
The generation of novel biology
Types of genes based on modifiability
Are misconceptions harmless?
Conclusion
Acknowledgments
References
Chapter 5. Genotype–phenotype considerations in neurogenetic disease
Abstract
Introduction
Genotype
Phenotype
Genotype–phenotype correlation: definition and clinical use
Penetrance
Expressivity
Clinical heterogeneity
Complex disease and polygenic risk
Genotype–phenotype considerations for the neurogenetic evaluation
Conclusions
Funding
Conflict of interest
References
Chapter 6. Immunogenetics of neurological disease
Abstract
Introduction
Lessons from immunogenetics
Immune cell states
Major histocompatibility complex
Neurodegeneration and the immune system
Neurologic adverse events from immunotherapy: role of immunogenetics
Immunosenescence
Immunogenetics and the future of neurologic disease
References
Further reading
Chapter 7. Pharmacogenomic approaches to the treatment of sporadic Alzheimer’s disease
Abstract
Genetic risk factors and sporadic Alzheimer’s disease
Genetic risk factors, cholinergic dysfunction, and Alzheimer’s disease
APOE4 and cholinomimetic drugs in Alzheimer’s disease
Experimental drugs and their relationship to the APOE4 genotype
Acetylcholinesterase and butyrylcholinesterase genetic variants in dementia
Pharmacogenomics of adverse side effects
Acknowledgments
References
Chapter 8. Application of mouse genetics to human disease: generation and analysis of mouse models
Abstract
Creating mouse models
Phenotypic analysis of mouse models
Summary
References
Chapter 9. DNA sequencing and other methods of exonic and genomic analyses
Abstract
DNA sequencing technologies
Application of next-generation sequencing to elucidating Mendelian-trait diseases
Search for de novo mutations based on whole-exome sequencing/whole-genome sequencing analyses of trios
References
Chapter 10. Association, cause, and causal association. Revision 2: playing the changes
Abstract
Considerations
Learning from infectious disease
Causal “guidelines” and observational versus experimental designs
A path forward and artificial intelligence
The progression of complexity into public health
References
Chapter 11. Adeno-associated virus-mediated gene therapy in central nervous system genetic disorders
Abstract
Introduction
Part I: development of adeno-associated virus as a central nervous system gene transfer vector
Part II: development of AAV-mediated gene therapy for CNS diseases
Part III: clinical translation, milestones, and challenges
Conclusion
Acknowledgments
References
Chapter 12. Genomics of human neurological disorders
Abstract
“-Omics”
Technology
Human variation
Clinical impact of human variation
Comparative genomics
Functional genomics
Single cell transcriptomics
Applying human genomics to understanding disorders of the nervous system
References
Chapter 13. CRISPR/Cas9-based genetic engineering for translational research in neurological disorders
Abstract
Introduction
CRISPR and its working mechanisms
DNA cleavage via conventional CRISPR/Cas9 in neurological disorders
The expanding family of CRISPR effectors and toolkits for gene editing
Challenges toward a fruitful translation of CRISPR technologies for clinical neurology
Concluding remarks
Acknowledgments
References
Chapter 14. Neural cells derived from pluripotent stem cells and directly induced from somatic cells
Abstract
Introduction
Direct induction of neural stem cells from somatic cells
Direct induction of neurons from somatic cells
References
Chapter 15. Neuroimaging in dementia
Abstract
Neuroimaging technologies
Alzheimer’s disease
Dementia with Lewy bodies
Frontotemporal dementia
Imaging vascular contributions to cognitive impairment and dementia
Recent efforts in the field of dementia
References
Chapter 16. Neuroethics
Abstract
Animal ethics
Research on human subjects
Diagnosis-related issues
Lifesaving and quality of life
Treatment versus enhancement
Neuroprivacy
Moral status “in the dish”
Brain death and disorders of consciousness
Personal identity
Neurodiversity
Conclusion
Chapter 17. Genetic counseling
Abstract
Introduction to genetic counseling
Components of genetic counseling and case preparation
Genetic testing
Ethical issues
Conclusion
References
Chapter 18. Antisense oligonucleotide drugs for neurological and neuromuscular diseases
Abstract
Introduction
Opportunities for ASOs in neuroscience
Mechanisms of action of ASOs
Chemical modification of ASOs
Potential adverse effects of ASOs
Pharmacokinetics/delivery of ASOs
Preclinical studies of ASOs in the central nervous system
Clinical development of ASOs
Conclusions
Disclosure statement
Acknowledgments
References
Chapter 19. Autophagy and neurological disorders
Abstract
Introduction to autophagy
Autophagy and brain health
Autophagy in neurodegenerative disorders
Alzheimer’s disease
Parkinson’s disease
Huntington’s disease
Amyotrophic lateral sclerosis
Autophagy and prion disease
Autophagy and stroke
Autophagy and multiple sclerosis
Conclusion: the potential of autophagy therapeutics in neurological disorders
References
Chapter 20. The aging brain
Abstract
Introduction
Clinically defining and characterizing healthy brain aging
Epidemiology of unhealthy brain aging
Brain aging through the lens of the hallmarks of aging
Brain aging interventions
Concluding statements and perspectives
References
Section II: Neurologic diseases
Chapter 21. Cerebral malformations
Abstract
Malformations of cortical development
Malformations related to abnormal proliferation of neurons and glia
Malformations due to abnormal neuronal migration
Malformations related to abnormal cortical organization
References
Chapter 22. Global developmental delay and intellectual disability
Abstract
Introduction
Diagnosis of global developmental delay and intellectual disability
Evaluation and investigation of individuals with global developmental delay or intellectual disability
Genetic etiologies
Disease mechanisms
Management
References
Chapter 23. Aging and dementia in Down syndrome
Abstract
Clinical features
Molecular genetics
Alzheimer disease mechanisms in Down syndrome
Factors affecting Alzheimer disease diagnosis
Management
Current research
Acknowledgments
References
Chapter 24. An overview of Rett syndrome
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Management
References
Chapter 25. Fragile X clinical features and neurobiology
Abstract
Summary
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Acknowledgments
References
Chapter 26. Neurological evaluation and management of autism spectrum disorder
Abstract
Summary
Medical testing
Analytical testing clinical and ancillary testing: imaging, physiological, electrodiagnostic
Clinical features
Fragile X syndrome
Molecular genetics
Rett syndrome
Natural history
Molecular genetics
Genotype–phenotype correlations
Angelman syndrome
Natural history
Molecular genetics
Disease mechanisms
Differential diagnosis—nongenetic causes of autism
Management
Pharmacotherapy
Conclusion
References
Chapter 27. Angelman syndrome
Abstract
Summary
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 28. The prion diseases
Abstract
Summary
Clinical features
Clinical subtypes of prion disease
Molecular genetics
Disease mechanisms
Differential diagnosis
Diagnostic studies
Management
References
Chapter 29. Leptin-related disorders of the nervous system
Abstract
Leptin as a link between metabolic and neurological disorders
Leptin functions
Leptin in neurodevelopment
Leptin in neurological disorders
Leptin replacement therapy in leptin disorders
References
Chapter 30. Genetics of autonomic disorders
Abstract
Introduction
Genetic mechanisms of autonomic dysfunction
Hereditary sensory autonomic neuropathies
Other inherited small fiber (sensory and autonomic) neuropathies
Familial autonomic ganglionopathy due to mutations of ganglionic AChR
Inherited disorders of catecholamine synthesis
Genetics of neurodegenerative autonomic disorders
Summary
References
Section III: Neurometabolic disorders
Chapter 31. The mitochondrial genome
Abstract
Mitochondrial origins
Genome organization
Mitochondrial Inheritance
Segregation and heteroplasmy
DNA replication
Transcription
Translation
Protein importation
Acknowledgments
References
Chapter 32. Mitochondrial disorders due to mutations in the mitochondrial genome
Abstract
Clinical features
Molecular genetic
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 33. Mitochondrial disorders due to mutations in the nuclear genome
Abstract
Clinical overview and history
Prevalence
Clinical presentation
Molecular genetics and disease mechanisms
Testing
Management
References
Chapter 34. Pyruvate dehydrogenase, pyruvate carboxylase, Krebs cycle, and mitochondrial transport disorders
Abstract
Pyruvate dehydrogenase deficiency
Pyruvate carboxylase deficiency
Disorders of the Krebs cycle
E3 deficiency
Succinate dehydrogenase deficiency
Fumarase deficiency
Mitochondrial transporter disorders
Adenine nucleotide translocator deficiency
Malate–aspartate shuttle deficiency
Voltage-dependent anion channels deficiency
Carnitine transporter deficiency
Acknowledgments
References
Chapter 35. Gaucher disease—neuronopathic forms
Abstract
Clinical features
Early treatments
Mode of inheritance and prevalence
Natural history and clinical syndromes
Typical specific features
Auditory dysfunction
Myoclonus
Pathophysiology
Differential diagnosis
References
Chapter 36. The Niemann–Pick diseases
Abstract
Summary
Clinical features and diagnostic evaluation
Neuroimaging and neurophysiologic studies
Cellular pathology
Type C Niemann–Pick disease
Biochemical findings
Brain immunochemical findings
Mechanism of disease
Molecular genetics
Animal models
Type C Niemann–Pick disease
Therapy
Type C Niemann–Pick disease
Conclusion
References
Chapter 37. GM2-gangliosidoses
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 38. Metachromatic leukodystrophy and multiple sulfatase deficiency
Abstract
Introduction
Clinical features
Natural history
Multiple sulfatase deficiency
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Therapies under investigation
References
Chapter 39. Krabbe disease: globoid cell leukodystrophy
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Acknowledgments
References
Chapter 40. Leukodystrophies—an overview
Abstract
Introduction
Classification and pathophysiology
Diagnosis
Treatment
References
Chapter 41. The mucopolysaccharidoses
Abstract
Summary
History
Clinical features
Management
References
Further reading
Chapter 42. The mucolipidoses
Abstract
Summary
Clinical features
Sialidosis types I and II
Biochemical and molecular studies
Galactosialidosis
Biochemical and molecular studies
Mucolipidosis II (I-cell disease)
Biochemical and molecular studies
Mucolipidosis III (pseudo-Hurler polydystrophy)
Biochemical and molecular studies
Mucolipidosis IV
Biochemical and molecular studies
Management
References
Chapter 43. Disorders of glycoprotein degradation: α-mannosidosis, β-mannosidosis, fucosidosis, sialidosis, and aspartylglycosaminuria
Abstract
Introduction
Biosynthesis and biodegradation of glycoproteins
Principle of treatment
Acknowledgments
References
Chapter 44. GM1 gangliosidosis, Morquio disease, galactosialidosis, and sialidosis
Abstract
Biochemistry of the B-gal, protective protein cathepsin A, and neuraminidase 1 complex
GM1 gangliosidosis and Morquio B disease
Galactosialidosis
Sialidosis
References
Chapter 45. Acid ceramidase deficiency: Farber lipogranulomatosis, spinal muscular atrophy associated with progressive myoclonic epilepsy and peripheral osteolysis
Abstract
Introduction
Clinical picture
Diagnosis
Pathology
Clinical genetics
Molecular genetics
Animal models
Therapy
Conclusion and future directions
References
Chapter 46. Wolman disease
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
References
Chapter 47. Lysosomal membrane disorders: lysosome-associated membrane protein-2 deficiency (Danon disease)
Abstract
Human muscle disorder due to lysosomal membrane defect
Danon disease
Clinical features
Muscle pathology
LAMP-2
LAMP-2 gene mutations
LAMP-2 knock-out mouse and other LAMP-2 deficiency models
Other autophagic vacuolar myopathies
Management
References
Further reading
Chapter 48. Fabry disease: α-galactosidase A deficiency
Abstract
Clinical features
Mode of inheritance, incidence, and prevalence
Natural history and clinical manifestations
Biochemical genetics
Molecular genetics
Disease pathology/pathophysiology
Differential diagnosis
Medical management
Summary
Acknowledgments
References
Chapter 49. Schindler disease: deficient α-N-acetylgalactosaminidase activity
Abstract
Introduction
Clinical features and diagnostic results
Neuropathology
Diagnostic evaluation
Biochemistry
Molecular genetics
Relation to other gene loci
Animal model
Therapy
Future research directions
Acknowledgment
References
Section IV: Metabolic disorders
Chapter 50. Organic acid disorders
Abstract
Summary
Clinical features
Mode of inheritance and prevalence
Natural history of organic acid disorders
Pathophysiology
Differential diagnosis
Molecular genetics in diagnosis
Testing
Treatment
References
Chapter 51. Glycogen and polyglucosan storage diseases
Abstract
Introduction
Clinical features
Diagnostic evaluation
Pathology
Biochemical findings
Molecular genetic findings
Animal models
Therapy
Conclusion
Acknowledgment
References
Chapter 52. Disorders of galactose metabolism
Abstract
Introduction
Classic galactosemia
Uridine diphosphate galactose 4-epimerase deficiency
Galactokinase deficiency
Galactose mutarotase deficiency
Fanconi–Bickel syndrome
Neonatal onset type II citrullinemia
Portosystemic venous shunting and hepatic arteriovenous malformations
References
Chapter 53. Inborn errors of amino acid metabolism
Abstract
Introduction
Classic organic acidemias
Maple syrup urine disease
Glutaric aciduria type I
Phenylketonuria and disorders of biopterin metabolism
Tyrosinemia type 1
Tyrosinemia type 2
Nonketotic hyperglycinemia
Homocystinuria
4-Hydroxybutyric aciduria
Canavan disease
Conclusion and future research directions
References
Chapter 54. Urea cycle disorders
Abstract
Summary
Clinical features
Neonatal presentation
Late-onset presentations
Disease-specific manifestations
Outcomes
Molecular genetics
Expression of urea cycle enzymes and nitrogen metabolism
Disease mechanisms/pathophysiology
Neurological and neuroimaging aspects
Differential diagnosis
Testing
Management
Diet management
Drug therapy
Transplantation
Current research
References
Chapter 55. Glucose transporter type I deficiency and other glucose flux disorders
Abstract
Overview of glucose transport
Clinical features of SGLT1 deficiency
Clinical features of GLUT2 deficiency
Clinical features of GLUT1 deficiency
Molecular genetics of GLUT1 deficiency
Disease mechanisms in GLUT1 deficiency
Animal models of GLUT1 deficiency
Differential diagnosis of GLUT1 deficiency
Testing for GLUT1 deficiency
Treatment of GLUT1 deficiency
Barriers to treatment development
Acknowledgments
References
Chapter 56. Maple syrup urine disease: biochemical, clinical, and therapeutic considerations
Abstract
Introduction
Clinical presentation of classic maple syrup urine disease
Neuropathology of maple syrup urine disease
Variant types of maple syrup urine disease
Genetics and prevalence
Macromolecular organization and component reactions
The thiamine-responsive phenotype is linked to the presence of mutant E2 proteins
Animal models for classic and intermediate maple syrup urine disease
Treatments of classic maple syrup urine disease
Domino liver transplantation in classical MSUD patients
Small-molecule inhibitors targeting branched-chain α-ketoacid dehydrogenase kinase
Gene therapy in MSUD model organisms
Concluding remarks
Acknowledgments
References
Chapter 57. Congenital disorders of N-linked Glycosylation
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Conclusion
References
Chapter 58. Disorders of glutathione metabolism
Abstract
Glutathione and the γ-glutamyl cycle
Disorders of enzymes in the γ-glutamyl cycle
Excitatory amino acid transporters
Disorders of EAAC1 leading to glutathione depletion
Neurodegenerative diseases leading to glutathione depletion
Neurodegenerative diseases and microRNA regulation of glutathione level
Conclusions
References
Chapter 59. Canavan disease
Abstract
Summary
Clinical features
Biochemical studies
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Epidemiology
Prevention/prenatal diagnosis
Management
Therapy
References
Chapter 60. Neurotransmitter disorders
Abstract
Summary
Disorders of monoamines
Defects of synthesis
Aromatic L-amino acid decarboxylase deficiency
Dopamine β-hydroxylase deficiency
Defects of catabolism
Defects of transport
Defects of cofactors
Guanosine triphosphate cyclohydrolase-I deficiency
Sepiapterin reductase deficiency
Disorders of γ-aminobutyric acid
Succinic semialdehyde dehydrogenase deficiency
GABA-transaminase deficiency
Glutamic acid decarboxylase deficiency
GABA receptor subunits and transporter-related diseases
Pyridoxine-related diseases
New categories of neurotransmission disorders
Disorders of the synaptic vesicle cycle
Glutamate neurotransmitter disorders
Glycine neurotransmitter disorders
Choline neurotransmitter disorders
Abbreviations
References
Chapter 61. Peroxisomal disorders
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Diagnostic testing
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
References
Chapter 62. Purines and pyrimidines
Abstract
Introduction
Disorders of purine metabolism
Disorders of pyrimidine metabolism
References
Chapter 63. The acute porphyrias
Abstract
Introduction
Pathophysiology
Clinical aspects
Diagnosis
Treatment
References
Index

Roger N. Rosenberg

Roger N. Rosenberg, MD is a graduate of Northwestern University Medical School, With Distinction, and was subsequently trained in Neurology with H. Houston Merritt, MD at the Neurological Institute, Columbia University, New York, was Chief Resident and then was a Post-Doctoral Fellow with Nobel Laureate Marshall Nirenberg at the NIH in the Laboratory of Biochemical Genetics. He is Board Certified by the American Board of Psychiatry and Neurology. He is holder of the Zale Distinguished Chair and Professor of Neurology and Neurotherapeutics at the University of Texas Southwestern Medical Center at Dallas since 1973 and developed the department for 18 years as Chair from 1973-1991. He described for the first time in 1975 Machado Joseph disease, an autosomal dominant cerebellar degeneration, which produces imbalance and impaired coordination, and showed it was due to a unique expansion of DNA in the causal gene. It is the most common inherited form of impaired coordination in the world and his research has provided a genetic marker to eliminate it in large families in future generations. He has served as the Founding Director of the UT Southwestern NIH funded Alzheimer’s Disease Center and Principal Investigator of the NIH Center Grant from 1987-2019. He directs an active laboratory effort in Alzheimer’s Disease. He is developing a DNA Aβ42 trimer vaccine for Alzheimer's disease for which he was awarded a US Patent "Amyloid Beta Gene Vaccines" in January 2009. It has been tested in mouse, transgenic mouse, New Zealand white rabbits and rhesus monkeys. The vaccine produces effective anti-Aβ42 peptide antibody levels and is non-inflammatory in all three species. The vaccine reduces by 40% Aβ42 peptide and by 50% tau and phospho-tau in the brains of 3X AD Tg mice, the two main pathologies of Alzheimer’s disease, with high levels of anti-Aβ42 antibody and with a non-inflammatory immune response. He is preparing now a Phase 1 Clinical trial Grant - First in Human to determine its effectiveness and safety in human subjects. He has published 297 original scientific articles, chapters, reviews, and editorials. He served as Editor in Chief from 1997 through 2017 for JAMA Neurology (formerly Archives of Neurology), a major international neurology journal, published by the American Medical Association. During his tenure, he raised the Impact Factor of the journal from 3.0 to 10.2, placing JAMA Neurology as #1 of all US publications in neurology. He is the founding editor of two of the landmark texts in neuroscience. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease, 5th edition, published in 2015 by Elsevier. The 6th edition will publish in 2020. The Atlas of Clinical Neurology, 4th edition, has just been published. He is a former President of the American Academy of Neurology, former Vice-President of the American Neurological Association, an Honorary Member of both organizations, and a Fellow of the American Association for the Advancement of Science. He received the first Science Medal in 2009 from the World Federation of Neurology for his contributions to neuro-genetics, for his original clinical and molecular genetics research on Machado-Joseph disease, and the development of the DNA Abeta42 trimer vaccine for Alzheimer’s disease.

Affiliations and expertise

Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology, Professor of Neurology and Neurotherapeutics, Founding Director, Alzheimer’s Disease Center Head, Section on Memory and Behavioral Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Juan M. Pascual

Juan M. Pascual, M.D., Ph.D., is the inaugural holder of The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases and also holds the Ed and Sue Rose Distinguished Professorship in Neurology. His laboratory research interests span virtually the entire field of neuroscience, including medical neuroscience, from molecular structure and function (including drug action), neural physiology and metabolism at the cellular, circuit and whole-brain level and neurogenetics, all of which is complemented with neurological patient care and clinical trials. Laboratory research greatly influences his clinical activities and patient observations guide his laboratory research direction. As a clinician, Dr. Pascual specializes in genetic and metabolic diseases of the nervous and neuromuscular systems of infants, children, and adults with a particular emphasis on complex diagnostic problems, second opinions for patients visiting from the rest of the U.S. and abroad, and in clinical trials. Dr. Pascual has special clinical research expertise in undiagnosed and rare diseases, glucose metabolism, mitochondrial, degenerative, and multi-organ disorders. Dr. Pascual is a tenured faculty member in four Departments at UT Southwestern Medical Center: Neurology and Neurotherapeutics, Physiology, Pediatrics, and the Eugene McDermott Center for Human Growth & Development / Center for Human Genetics. He is also Director of the Rare Brain Disorders Program (Clinic and Laboratory). He is also a member of the Division of Pediatric Neurology, of the graduate Ph.D. programs in Neuroscience and Integrative Biology, and of the postgraduate clinical training programs in Neurology, Pediatric Neurology, Pediatrics, and Medical Genetics. He teaches at UT Southwestern Medical School. In addition, Dr. Pascual is an adjunct professor in the Department of Biological Sciences at the School of Natural Sciences and Mathematics, The University of Texas at Dallas. Dr. Pascual directs a highly collaborative research laboratory and is credentialed campus-wide at Children's Medical Center Dallas, UT Southwestern University Hospitals and Clinics, and Parkland Memorial Hospital, where he consults on inpatients and outpatients with particularly complex or severe diseases. Much of his research is funded by the National Institutes of Health. Dr. Pascual received his M.D. degree with unique distinction from the Universidad de Granada, Spain, one of the oldest universities in the world, founded in 1349 by Yusuf I, Sultan of Granada and one of the builders of the Alhambra. He received his Ph.D. degree in Molecular Physiology and Biophysics from Baylor College of Medicine in Houston, Texas, under Arthur M. Brown, M.D., Ph.D., McCollum Professor and Chair. His postdoctoral research was conducted under Arthur Karlin, Ph.D., Higgins Professor and Director of the Center for Molecular Recognition, College of Physicians and Surgeons of Columbia University and, later, at the Colleen Giblin Research Laboratories for Pediatric Neurology at the same institution under a Neurological Sciences Academic Development Award from the National Institute of Neurological Disorders and Stroke. He also received residency training in Pediatrics at Washington University School of Medicine - St. Louis Children's Hospital and in Neurology and Pediatric Neurology at the Neurological Institute of New York - Columbia University Medical Center. He received certification in Neurology with Special Qualification in Child Neurology from the American Board of Psychiatry and Neurology.

Affiliations and expertise

Dept Neurology and Neurotherapeutics, Physiology and Pediatrics; McDermott Ctr for Human Growth and Dev/Ctr for Human Genetics, Univ of Texas Southwestern Medical Ctr, Dallas, TX, USA

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