Wilson Disease

1st Edition, Volume 142 - April 18, 2017
Editors: Anna Czlonkowska, Michael Schilsky
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 4 - 6 3 6 2 5 - 6
eBook ISBN:
9 7 8 - 0 - 4 4 4 - 6 3 6 2 7 - 0

Wilson Disease provides a comprehensive guide on this inherited genetic disorder that has devastating consequences for both the liver and neurologic/psychiatric health. This dise… Read more

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Wilson Disease provides a comprehensive guide on this inherited genetic disorder that has devastating consequences for both the liver and neurologic/psychiatric health. This disease is of increasing interest to neurologists, hepatologists, and geneticists, but when the disease is diagnosed early, it is treatable, with patients living normal lives.

This volume describes the molecular pathophysiology of WD and the clinical and pathological effects of copper. Separate sections address both diagnosis and medical and surgical approaches to treatment. Both adult and pediatric perspectives on diagnosis and treatment are addressed, and a section on genetics highlights advances in molecular diagnostics. Patient support groups that can aid in coping with this disease are also discussed, as are animal models for those interested in basic research on cell biology, pathophysiology, and treatment.

Chapter 1: History of Wilson disease: a personal account
J M. Walshe

Abstract

Chapter 2: Epidemiology and introduction to the clinical presentation of Wilson disease
Christine Lo and Oliver Bandmann

Abstract
Introduction
Biochemical screening for the study of prevalence
Modern genetics studies
Population isolates
Genetic versus clinical prevalence
Clinical course
Conclusion

Chapter 3: The genetics of Wilson disease
Sihoun Hahn

Abstract
Introduction
Inheritance
ATP7B gene and atpase
Molecular structure of ATP7B
ATP7B (P-type atpase) protein structure and function
Variants in the ATP7B gene
Regional gene frequency
Genotype–phenotype correlation
Clinical molecular diagnosis
Population screening
Conclusion

Chapter 4: Genetic and environmental modifiers of Wilson disease
Valentina Medici and Karl Heinz Weiss

Abstract
Introduction
COMMD1 gene
ATOX1 gene
XIAP gene
APOE gene
HFE gene and metal transporter genes DMT1 and ATP7A
MTHFR gene
Human prion gene
Gender
Iron
Methyl groups
Other dietary factors
Summary and conclusion
Abbreviations

Chapter 5: Pathogenesis of Wilson disease
Petr Dusek, Radan Bruha and Ivo Florin Scheiber

Abstract
Introduction
Copper metabolism
ATP7B
Liver disease
Neuropsychiatric disease
Other symptoms
Acknowledgments

Chapter 6: Animal models of Wilson disease
Dominik Huster and Valentina Medici

Abstract
Introduction
Copper toxicity and liver disease in rodent models of wilson disease
Comparison of rodent models for wilson disease
Other animal models of copper accumulation and toxicity in the liver and brain
Research perspectives and future therapy developments
Abbreviations
Acknowledgment

Chapter 7: Wilson disease – liver pathology
Maciej Pronicki

Abstract
Pathology of wilson disease
Light microscopic detection of copper deposits
Ultrastructure
Summary

Chapter 8: Wilson disease: brain pathology
France Woimant, Aurelia Poujois and Jacqueline Mikol

Abstract
Introduction
Pathologic changes
Copper in the brain
Iron, manganese, and other causative factors
Differential diagnosis
Conclusions
Acknowledgment

Chapter 9: Hepatic features of Wilson disease
Michael L. Schilsky, Aftab Ala and Salih Boga

Abstract
Hepatic features of Wilson disease
The spectrum of liver disease in Wilson disease
Physical examination and laboratory findings
Noninvasive assessment of Wilson disease
Wilson disease patients with severe liver disease
Concomitant liver disease with Wilson disease
Hepatocellular carcinoma and Wilson disease
Prognosis of patients with Wilson disease
Conclusions

Chapter 10: Wilson disease: neurologic features
Anna Czlonkowska, Tomasz Litwin and Grzegorz Chabik

Abstract
Introduction
The neurologic classifications of disease
Tremor
Dystonia
Parkinsonism
Ataxia
Chorea
Dysarthria
Dysphagia
Drooling
Gait and posture
Epilepsy
Neuropathy
Autonomic impairment
Olfactory dysfunction
Other neurologic features of wilson disease
Ophthalmologic signs of wilson's disease
Clinical scales assessing neurologic deficits in wilson disease
Neuroimaging in wilson disease
Other examinations
Conclusions

Chapter 11: Cognitive and psychiatric symptoms in Wilson disease
Paula C. Zimbrean and Joanna Seniow

Abstract
Introduction
Physiologic basis for psychiatric and cognitive symptoms in wilson disease
Evaluation of cognitive impairment and psychiatric symptoms in wilson disease
Cognitive function in patients with wilson disease
Psychiatric presentations in wilson disease
Treatment of psychiatric symptoms in wilson disease
Conclusion

Chapter 12: Wilson disease in children
Eve A. Roberts and Piotr Socha

Abstract
Developmental physiology of copper
Age incidence
Clinical presentations
Diagnosis
Treatment
Screening: newborns; first-degree relatives
Look-alike pediatric disorders
Genotype–phenotype correlation
Summary

Chapter 13: Other organ involvement and clinical aspects of Wilson disease
Karolina Dziezyc, Tomasz Litwin and Anna Czlonkowska

Abstract
Introduction
The kidneys
The osteoarticular system
Cardiovascular system
Endocrinology
Hematology
Dermatology
Other clinical aspects of wilson disease

Chapter 14: Diagnosis of Wilson disease
Peter Ferenci

Abstract
Introduction
Physical signs and clinical presentations
Liver disease
Neurologic disease
Laboratory parameters
Acute liver failure due to wilson disease
Family screening
Differential diagnosis
Leipzig score

Chapter 15: Wilson disease – currently used anticopper therapy
Anna Czlonkowska and Tomasz Litwin

Abstract
Pharmacologic treatment of wilson disease
Current drugs used in wilson disease treatment
Supplementary therapies for wilson disease
Special clinical situations during wilson disease treatment
Conclusion and general rules for treating wilson disease

Chapter 16: Liver transplantation for Wilson disease
Michael L. Schilsky

Abstract
Introduction
Indications for liver transplantation
Management of the patient with acute liver failure due to Wilson disease
Liver transplantation for chronic liver failure and end-stage liver disease due to Wilson disease
Liver transplantation for neuropsychiatric manifestations of Wilson disease
Organs allocation policy for liver transplantation and Wilson disease
Options for liver transplantation for Wilson disease
Outcomes and monitoring after liver transplantation
Immunosuppression after liver transplantation in Wilson disease patients
Conclusion: the future of liver transplantation for Wilson disease

Chapter 17: Wilson disease: symptomatic liver therapy
Wolfgang Stremmel and Karl Heinz Weiss

Abstract
Introduction
Steatosis, liver fibrosis, and compensated liver cirrhosis
Decompensated liver cirrhosis
Conclusion

Chapter 18: Symptomatic treatment of neurologic symptoms in Wilson disease
Tomasz Litwin, Petr Dusek and Anna Czlonkowska

Abstract
Introduction
Tremor
Dystonia
Parkinsonism
Chorea
Neurosurgical treatment of wilson disease
Supportive therapy
Effect of liver transplantation on neurologic wd symptoms
Conclusions
Acknowledgments

Chapter 19: Novel perspectives on Wilson disease treatment
Christian Rupp, Wolfgang Stremmel and Karl Heinz Weiss

Abstract
Introduction
Response-guided therapy
Tetrathiomolybdate
Other drugs
Mutation-specific therapy
Gene transfer
Hepatocyte/tissue transfer
Conclusion

Chapter 20: Patient support groups in the management of Wilson disease
Michael L. Schilsky and Mary L. Graper

Abstract
Introduction on patient support groups for rare diseases
History and profile of the wilson disease association
Other worldwide wilson disease organizations
Other organizations that support wilson disease
Specific challenges faced in the support of wilson disease patients
The patient perspective
Future goals
Disclosures

Anna Czlonkowska

Anna Członkowska MD Prof earned her Diploma of Medicine at Warsaw Medical Academy before she completed her Doctor of Medicine at the Institute of Psychiatry and Neurology, Warsaw. She received additional training at the Boards of Clinical Neurology at the Institute of Psychiatry and Neurology in Warsaw and Habilitation in Neurology at the Warsaw Medical Academy. She has also received several prestigious fellowships, ranging from a British Council Grant for Neuroimmunology to a Neurobiology Fellowship funded by a Max Planck Society Grant. Between 1985-2013, she served as Professor and Head of the Second Department of Neurology at the Institute of Psychiatry and Neurology in Warsaw. She currently is the professor in this department and Head of the Study Group at the Department of Experimental and Clinical Pharmacology, Medical University of Warsaw. Additionally, Członkowska served as a member of the International Consortium at EUROWILSON. Since 1969, Członkowska has not only cared for a large cohort of 850 patients with Wilsons Disease, created a research database to document their clinical features and evaluate the clinical course of WD (with a focus on the efficacy of current therapies), but has also completed basic research on the pathogenesis of WD. She collaborates with WD centers across Europe.). Her contributions to clinical science extend well beyond Wilson’s Disease and she has been active in research and clinical trials in stroke, multiple sclerosis and neurorehabilitation. Finally, Czlonkowska has supported the career development of many young clinicians and clinical academics whose success owes much to her leadership and support.

Affiliations and expertise

2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland

Michael Schilsky

Michael Schilsky, MD, became medical director of liver transplantation at Yale-New Haven Hospital in 2007, with appointments in medicine and surgery at the Yale School of Medicine. Dr. Schilsky received his medical degree from the University of Chicago, Pritzker School of Medicine. He completed his residency and fellowship in gastroenterology and research training in liver diseases at Albert Einstein College of Medicine and Montefiore Medical Center. His clinical and research interests include transplant hepatology, inherited metabolic disorders of the liver, Wilson disease and hemochromatosis. Dr. Schilsky previously served as director of the liver medicine clinic at the Recanati/Miller Transplantation Institute at Mount Sinai Medical Center and medical director for liver transplantation at the New York Weill Cornell Medical Center, where he developed a comprehensive program for the care and evaluation of liver transplant patients. Dr. Schilsky coauthored the AASLD practice guidelines for Wilson disease and is author of numerous original manuscripts and reviews.

Affiliations and expertise

Medical Director, Adult Liver Transplant, Yale-New Haven Transplantation Center, New Haven, CT, USA

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Anna Czlonkowska

Michael Schilsky