Wilson's Disease

by Brewer, George J.

• ISBN13: 9780792373544
• ISBN10: 0792373545
• Format: Hardcover
• Copyright: 2001-06-01
• Publisher: Kluwer Academic Pub

Summary

Movement disorder specialists, general neurologists, hepatologists, general gastroenterologists, and psychiatrists are the specialists who will most likely see some Wilson's disease patients during their careers. See them - yes. Recognize and diagnose them - maybe. If you are in one of these specialties, and a patient with tremor, hepatitis, cirrhosis, apparent Parkinsonism, or mood disorder, is referred to you, will you appropriately recognize the possibility that the underlying diagnosis may be Wilson's disease? Wilson's disease is both treatable and reversible, and commonly misdiagnosed. This book aims to change this with comprehensive coverage of every aspect of Wilson's disease, from well-catalogued, easy-to-use clinical diagnostic tools to treatment methods to molecular biology. Dr. Brewer is the world's leading expert on Wilson's disease, seeing and caring for over 300 patients with the disease during the last 20 years. He is a professor of human genetics at the University of Michigan.

Table of Contents

List of Figures	xvii
List of Tables	xix
Forward	xxi
Preface	xxiii
Acknowledgments	xxvii
Overview of the Disease for the Clinician	1	(8)
Introduction	1	(1)
Cause of Wilson's disease	2	(1)
Inheritance	3	(1)
Clinical Presentations	3	(1)
Recognition Problem	4	(1)
Some Screening Tests are Accurate	5	(1)
Diagnosis is Usually Straightforward	5	(1)
Treatment and Management Concepts	6	(1)
Monitoring and Compliance	6	(1)
Prognosis	7	(2)
The Clinician's Challenge: Recognizing Wilson's Disease	9	(20)
Introduction	9	(1)
The Neurological Presentation	10	(6)
If Your Patients Has Movement Disorder-Type Neurological Symptoms (Important Ones Are Dysarthria, Tremor, Dystonia, and Incoordination)	10	(4)
Disasters and Near Disasters Caused by Clinicians Failing to Diagnose Wilson's Disease Patients with a Neurologic Presentation	14	(1)
Full-blown Neurologic Syndrome Unrecognized	14	(1)
Tremor Unrecognized	15	(1)
Parkinsonism-like Syndrome, Unrecognized at First	15	(1)
The Hepatic Presentation	16	(5)
Hepatitis and Episodic Hepatitis	16	(1)
Cirrhosis	17	(1)
Hepatic Failure	18	(1)
Severe Hepatic Failure	19	(1)
Mild Hepatic Failure	20	(1)
Intermediate Hepatic Failure	21	(1)
Disasters Caused by Clinicians Failing to Diagnose Wilson's Disease Patients with Hepatic Presentations	21	(1)
Chronic Hepatitis and Liver Failure Unrecognized	21	(1)
Cirrhosis, Hepatic Failure, and Family History Unrecognized	21	(1)
The Behavioral Change Presentation	21	(3)
Recognition of Wilson's Disease by Psychiatrists-The Good, and the Bad	24	(1)
The Presymptomatic Patient	24	(2)
Disasters Related to Screening Presymptomatic Patients	25	(1)
A Partial Disaster When a Physician Ignores Wilson's Disease Screening Data	25	(1)
Two Deaths, at Least One of Them Unnecessary	25	(1)
Other Situations in Which Wilson's Disease May be Present	26	(1)
Key Points with Respect to Recognition of Possible Wilson's Disease	27	(2)
Simple Approaches to Screening and Definitive Diagnosis	29	(20)
Introduction	29	(1)
Screening Tests and Procedures	29	(7)
The 24-Hour Urine Copper Assay	29	(5)
Kayser-Fleischer Ring Examination	34	(1)
Serum Ceruloplasmin Assay	34	(1)
Not Very Useful and/or Confusing Tests	35	(1)
How to Screen Patients for Wilson's disease	36	(6)
Neurologic/Psychiatric Presentation	36	(2)
Hepatic Presentation	38	(1)
Presymptomatic Patients	39	(3)
Making a Definitive Diagnosis of Wilson's Disease	42	(5)
Definitive Diagnosis Without a Liver Biopsy	42	(1)
Liver Biopsy with Measurement of Quantitative Copper	42	(2)
Diagnostic Dilemmas	44	(1)
Long-Standing Hepatic Failure or Obstruction	44	(3)
Other Diagnostic Dilemmas	47	(1)
Disasters and Near Disasters Related to Screening and Diagnostic Tests	47	(2)
Serum Copper Levels Misinterpreted	47	(1)
Liver Copper Assay in Error	48	(1)
DNA Mutation Test, Misinterpreted	48	(1)
Description of the Anticopper Drugs Which are Used in Wilson's Disease Therapy	49	(20)
Introduction	49	(1)
Zinc	49	(10)
Mechanism of Anticopper Action of Zinc	49	(2)
Main Uses of Zinc in Wilson's Disease	51	(2)
Evidence of Uniform Efficacy of Zinc in Wilson's Disease	53	(2)
An Unusual Case of Non-Compliance With Maintenance Zinc Therapy	55	(1)
Toxicity of Zinc	56	(1)
Monitoring Zinc Therapy	57	(2)
Trientine	59	(3)
Mechanism of Anticopper Action of Trientine	59	(1)
Main Uses of Trientine in Wilson's Disease	59	(1)
Evidence of Uniform Efficacy of Trientine in Wilson's Disease	59	(1)
Toxicity of Trientine	60	(1)
Monitoring Trientine Therapy	61	(1)
Tetrathiomolybdate	62	(3)
Mechanism of Anticopper Action of Tetrathiomolybdate (TM)	62	(1)
Main Use of Tetrathiomolybdate in Wilson's Disease	63	(1)
Evidence of Efficacy of Tetrathiomolybdate in the Initial Treatment of Neurologic Wilson's Disease	63	(1)
Toxicity of Tetrathiomolybdate	64	(1)
Monitoring Tetrathiomolybdate Therapy	65	(1)
Penicillamine	65	(3)
Mechanism of Anticopper Action of Penicillamine	62	(1)
Main Uses of Penicillamine in Wilson's Disease	62	(4)
Evidence of Uniform Efficacy of Penicillamine in Wilson's Disease	66	(1)
Toxicity of Penicillamine	67	(1)
Monitoring Penicillamine Therapy	68	(1)
Other Anticopper Drugs	68	(1)
Overview of Management for the Clinician: What's Important and What's Not	69	(10)
Introduction	69	(1)
Anticopper Drug Therapy Overview-Important	70	(3)
Keys to Successful Initial Therapy	70	(1)
Drug Choice	70	(1)
Drug Dose and Directions for Use	70	(1)
Monitoring for Drug Toxicity	70	(1)
Monitoring for Copper and/or Zinc Response (Compliance)	71	(1)
Keys to Successful Maintenance Therapy	71	(1)
Drug Choice	71	(1)
Drug Dose and Directions for Use	71	(1)
Monitoring for Drug Toxicity	72	(1)
Monitoring for Copper Response (Compliance)	72	(1)
Diet-Generally Not Important	73	(1)
Drinking Water-Occasionally Important	74	(1)
Patients Signs and Symptoms-Always Important	74	(5)
Hepatic Complications and Symptomatology	74	(2)
Neurologic Complications and Symptomatology	76	(1)
Psychiatric Complications and Symptomatology	77	(2)
Initial Treatment of Patients Who Present With Liver Disease	79	(18)
Introduction	79	(1)
Initial Therapy of Patients with Hepatic Failure	79	(15)
Review of Severe, Intermediate, and Mild Hepatic Failure	79	(2)
Triaging Patients for Hepatic Transplantation Versus Initial Medical Therapy	81	(4)
Hepatic Transplantation in Wilson's Disease	85	(1)
Indications for Hepatic Transplantation	85	(1)
Non-indications for Hepatic Transplantation	86	(2)
Anticopper Therapy While Awaiting Transplantation	88	(1)
Medical Therapy for Mild Hepatic Failure	89	(2)
Medical Therapy for Intermediate Hepatic Failure	91	(2)
A Disaster Resulting From a Failure to Adequately Reevaluate the Status of a Patient with Intermediate Hepatic Failure During Medical Therapy	93	(1)
Initial Therapy of Patients With Hepatitis	94	(3)
Initial Therapy of Patients With Cirrhosis	95	(2)
Initial Treatment of Patients Who Present With Neurological and/or Psychiatric Disease	97	(8)
Introduction	97	(1)
Neurological Worsening of Patients With Initial Penicillamine Therapy	98	(1)
Recommended Therapy-Tetrathiomolybdate	99	(3)
Method of Therapy	99	(1)
Results in an Open Study	100	(1)
Potential for Accessing Tetrathiomolybdate Therapy	101	(1)
Alternative Therapies	102	(3)
Zinc	102	(1)
Trientine	102	(3)
Maintenance Therapy	105	(12)
Introduction	105	(1)
Definition of Maintenance Therapy	105	(1)
Objectives of Maintenance Therapy	105	(1)
Recommended Maintenance Therapy-Zinc	106	(8)
Method of Therapy	106	(1)
Dietary Recommendations	107	(1)
Monitoring Zinc Therapy	108	(1)
Zinc Side Effects	109	(1)
Overtreatment	109	(1)
Results of Zinc Therapy in a Large Series of Patients	110	(4)
Alternative Maintenance Therapy	114	(3)
Trientine	114	(1)
Penicillamine	115	(2)
Therapy of the Presymptomatic, the Pediatric, and the Pregnant Patient	117	(10)
Therapy for the Presymptomatic Patient	117	(4)
Definition of Presymptomatic Patient	117	(1)
Usual Methods of Ascertaining Presymptomatic Patients	117	(1)
Recommended Therapy for the Presymptomatic Patient-Zinc	118	(1)
Alternative Therapy for the Presymptomatic Patient	118	(2)
Near Disaster and a Disaster Using Penicillamine Therapy in Initial Therapy of Presymptomatic Patient	120	(1)
Therapy for the Pediatric Patient	121	(2)
Introduction	121	(1)
Evidence for Early Disease and Therefore a Rationale for Early Treatment	121	(1)
Need to Avoid Overtreatment with Anticopper Agents in Children with Wilson's Disease	122	(1)
Recommended Therapy for the Pediatric Patient-Zinc	122	(1)
Alternative Therapy for the Pediatric Patient	122	(1)
Therapy for the Pregnant Patient	123	(4)
Need to Maintain Therapy During Pregnancy	123	(1)
Teratogenicity of Anticopper Therapy	124	(1)
Recommended Therapy for the Pregnant Patient-Zinc	124	(1)
Alternative Therapy for the Pregnant Patient-Trientine	124	(3)
Risk Factors During Maintenance Therapy and Prognosis	127	(8)
Introduction	127	(1)
A General Risk Factor-Poor Compliance	127	(4)
Disasters Related to Poor Compliance With Anticopper Therapy	130	(1)
Hepatic Risk Factors	131	(1)
Variceal Bleeding	131	(1)
Hepatic Failure	132	(1)
Neurological Risk Factors	132	(1)
Aspiration	132	(1)
Infection	133	(1)
Accidents	133	(1)
Psychiatric Risk Factors	133	(1)
Suicide	133	(1)
Prognosis	133	(2)
Disease Pathogenesis and Genetics	135	(14)
Introduction	135	(1)
Does Copper Toxicity Cause Wilson's Disease?	135	(1)
Normal Copper Handling	136	(1)
Defective Biliary Excretion of Copper in Wilson's Disease	136	(1)
The Genetics of Wilson's Disease	137	(6)
Gene Defect in Wilson's Disease	139	(4)
From Gene Defect to Copper Accumulation, Organ Damage, and Symptoms	143	(3)
Important Pathogenic Questions	144	(2)
Animal Models	146	(1)
Summary of Our Knowledge of Pathogenesis	147	(2)
Disease Pathology	149	(8)
Introduction	149	(1)
The Nature of Copper Toxicity	149	(2)
Liver Pathology	151	(1)
Brain Pathology	152	(1)
Pathology in Other Organs	153	(2)
The Female Reproductive System	153	(1)
The Skeletal System	153	(1)
The Kidneys	154	(1)
The Eyes	155	(1)
The Heart	155	(1)
Summary	155	(2)
History, Important Milestones, and the Future	157
Introduction	157
History of Wilson's Disease	157
Historical Milestones in Wilson's Disease	160
Future Challenges	160
Recognition	160
Better Screening Methods	162
Improved Compliance	163
Improved Therapy	163
Improved Understanding of Gene Function	164
Summary	164