Wilson’s Disease: A Clinician’s Guide to Recognition, Diagnosis, and Management

205 Pages·2001·7.774 MB·English

by  George J. Brewer (auth.)

WILSON'S DISEASE
A Clinician 's Guide to Recognition,
Diagnosis, and Management
WILSON'S DISEASE
A Clinician 's Guide to Recognition,
Diagnosis, and Management
By
George J. Brewer
University ofM ichigan Medical School
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data
Brewer, George J., 1930-
Wilson's disease: a clinician's guide to recognition, diagnosis, and management / by
George 1. Brewer.
p. ;cm.
lncludes bibliographical references and index.
ISBN 978-1-4613-5657-8 ISBN 978-1-4615-1645-3 (eBook)
DOI 10.1007/978-1-4615-1645-3
1. Hepatolenticular degeneration. 1. Title.
(DNLM: 1. Hepato1enticular Degeneration---<iiagnosis. 2. Hepatolenticular
Degeneration-therapy. WI 740 B847w 2001)
RC394.H4 B74 2001
616.3 '99---<ic21
2001023682
Copyright © 2001 Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2001
Softcover reprint ofthe hardcover lst edition 2001
AII rights reserved. No part ofthis publication may be reproduced, stored in a retrieval
system or transmitted in any form or by any means, mechanical, photo-copying,
recording, or otherwise, without the prior written permission ofthe publisher,Springer
Science +Business Media, LLC.
Printed an acid-free paper.
Dedication
I dedicate this mono graph to patients with Wilson's disease, particularly
those I have had the opportunity to work with, and who have provided
inestimable help in our joint efforts to improve the diagnosis and management
of this disease. I dedicate it also to the Wilson's Disease Association, which
contributes invaluable assistance through its pro grams designed for patients
and their families.
Chapter Guide
Chapter 1. Overview of the Disease for the Clinieian ....................... 1
Chapter 2. The Clinician's Challenge: Reeognizing Wilson's
Disease ........................................................... 9
Chapter 3. Simple Approaehes to Screening and Definitive
Diagnosis ...................................................... 29
Chapter 4. Deseription ofthe Anticopper Drugs Whieh are Used
in Wi1son's Disease Therapy .............................. ..49
Chapter 5. Overview of Management for the Clinieian: What' s
Important and What's Not.. ................................. 69
Chapter 6. Initial Treatment ofPatients Who Present with
Liver Disease .................................................. 79
Chapter 7. Initial Treatment of Patients Who Present with
Neurologie andlor Psychiatrie Disease .................... 97
Chapter 8. Maintenanee Therapy ............................................ 105
Chapter 9. Therapy of the Presymptomatie, the Pediatrie, and the
Pregnant Patient ............................................. 117
Chapter 10. Risk Faetors During Maintenanee Therapy and
Prognosis ..................................................... 127
Chapter 11. Disease Pathogenesis and Genetics ............................ 135
Chapter 12. Disease Patho10gy ................................................ 149
Chapter 13. History, Important Milestones, and the Future ............... 157
Table of Contents
List of Figures .......................................................................x vii
List of Tables. ......................................................................... xix
Forward. ..............................................................................x xi
Preface. ..............................................................................x xiii
Acknowledgments ................................................................. xxvii
1. Overview ofthe Disease for the Clinician .....................................1
Introduction .................................................................... 1
Cause ofWilson's disease ................................................... 2
Inheritanee ..................................................................... 3
Clinieal Presentations ......................................................... 3
Reeognition Problem ......................................................... 4
Some Screening Tests are Accurate ....................................... .5
Diagnosis is Usually Straightforward ....................................... 5
Treatment and Management Coneepts .....................................6
Monitoring and Complianee .................................................6
Prognosis ....................................................................... 7
2. The Clinician's Challenge: Recognizing Wilson's Disease ................9
Introduetion ....................................................................9
The Neurologieal Presentation ............................................. 10
IfYour Patient Has Movement Disorder-Type Neurologieal
Symptoms (Important Ones Are Dysarthria, Tremor,
Dystonia, and Ineoordination) .................................. .10
Disasters and Near Disasters Caused by Clinieians FaiIing to
Diagnose Wilson's Disease Patients with aNeurologie
Presentation .................................................... 14
Full-blown Neurologie Syndrome Unreeognized .................. 14
Tremor Unreeognized .................................................. 15
Parkinsonism-like Syndrome, Unreeognized at First. ............. 15
The Hepatic Presentation .................................................. 16
Hepatitis and Episodie Hepatitis ...................................... 16
Cirrhosis ................................................................. 17
Hepatie Failure .......................................................... 18
Severe Hepatie Failure ............................................ 19
Mild Hepatie Failure ............................................. .20
x Wilson's Disease
Intermediate Hepatic Failure ...... , ..................... , ... , .. 21
Disasters Caused by Clinicians Failing to Diagnose
Wilson's Disease Patients with Hepatic Presentations ........ 21
Chronic Hepatitis and Liver Failure Unrecognized ........... 21
Cirrhosis, Hepatic Failure, and Family
History Unrecognized ................................... 21
The Behavioral Change Presentation .......................................... 21
Recognition ofWilson's Disease by Psychiatrists-
The Good, and the Bad ................................................ 24
The Presymptomatic Patient ................................................... .24
Disasters Related to Screening Presymptomatic Patients ............. .25
A Partial Disaster When a Physician Ignores Wilson's
Disease Screening Data ........................................... 25
Two Deaths, at Least One ofThem Unnecessary .................. 25
Other Situations in Which Wilson's Disease May be Present. ............ .26
Key Points with Respect to Recognition of Possible
Wilson's Disease ............................................................ 27
3. Simple Approaches to Screening and Definitive Diagnosis •.............2 9
Introduction .......................................................................2 9
Screening Tests and Procedures ................................................ 29
The 24-Hour Urine Copper Assay ......................................... 29
Kayser-Fleischer Ring Examination ...................................... .34
Serum Ceruloplasmin Assay .............................................. .34
Not Very Useful and/or Confusing Tests ................................ .35
How to Screen Patients for Wilson's disease ................................ 36
NeurologiclPsychiatric Presentation ...................................... 36
Hepatic Presentation ......................................................... 38
Presymptomatic Patients ................................................... 39
Making a Definitive Diagnosis ofWilson's Disease ........................ .42
Definitive Diagnosis Without a Liver Biopsy .......................... .42
Liver Biopsy with Measurement of Quantitative Copper ............. .42
Diagnostic Dilemmas ...................................................... .44
Long-Standing Hepatic Failure or Obstruction .................... .44
Other Diagnostic Dilemmas .......................................... .47
Disasters and Near Disasters Re1ated to Screening and
Diagnostic Tests ............................................................. .47
Serum Copper Levels Misinterpreted .................................... .47
Liver Copper Assay in Error .............................................. .48
DNA Mutation Test, Misinterpreted ..................................... .48
Contents xi
4. Description ofthe Anticopper Drugs Which are Used in Wilson's
Disease Therapy ........•........•...........................•....•........•....4 9
Introduetion .......................................................................4 9
Zine ................................................................................4 9
Meehanism of Anticopper Action of Zinc ............................... .49
Main U ses of Zine in Wilson' s Disease ................................. .51
Evidenee ofUniform Effieaey of Zinc in Wilson's Disease ........... 53
An Unusual Case ofNon-Complianee With Maintenanee
Zine Therapy ............... , ...................................... .55
Toxieity of Zine ..............................................................5 6
Monitoring Zinc Therapy ................................................... 57
Trientine ........................................................................... 59
Meehanism of Anticopper Action ofTrientine .......................... 59
Main Uses ofTrientine in Wilson's Disease ............................. 59
Evidence ofUniform Efficacy ofTrientine in Wilson's Disease ...... 59
Toxieity ofTrientine ......................................................... 60
Monitoring Trientine Therapy ............................................. 61
Tetrathiomolybdate .............................................................. 62
Meehanism of Anticopper Action ofTetrathiomolybdate (TM) ... , .. 62
Main Use ofTetrathiomolybdate in Wilson's Disease .................. 63
Evidence ofEfficacy ofTetrathiomolybdate in the Initial
Treatment ofNeurologie Wilson's Disease ......................... 63
Toxicity ofTetrathiomolybdate ............................................ 64
Monitoring Tetrathiomolybdate Therapy ................................ 65
Penicillamine ...................................................................... 65
Mechanism of Anticopper Action ofPenicillamine .....................6 2
Main Uses ofPenicillamine in Wilson's Disease .......................6 2
Evidenee ofUniform Effieaey ofPenicillamine in
Wilson's Disease ........................................................ 66
Toxicity ofPenieillamine ................................................... 67
Monitoring Penicillamine Therapy ........................................ 68
Other Anticopper Drugs ......................................................... 68
5. Overview ofManagement for the Clinician: What's
Important and What's Not •.•......•....•.•..................•..•...••........6 9
Introduction .......................................................................6 9
Anticopper Drug Therapy Overview-Important.. .......................... 70
Keys to Successful Initial Therapy ........................................7 0
Drug Choiee .............................................................7 0
Drug Dose and Direetions for Use ....................................7 0
Monitoring for Drug Toxieity .........................................7 0
Monitoring for Copper and/or Zine Response (Complianee) ..... 71
xii Wilson's Disease
Keys to Sueeessful Maintenanee Therapy ................................ 71
Drug Choiee ............................................................. 71
Drug Dose and Direetions for U se .................................... 71
Monitoring for Drug Toxieity ......................................... 72
Monitoring for Copper Response (Complianee) .................... 72
Diet-Generally Not Important ................................................ 73
Drinking Water-Oeeasionally Important .................................... 74
Patients Signs and Symptoms-Always Important .......................... 74
Hepatie Complieations and Symptomatology ........................... 74
Neurologie Complieations and Symptomatology ....................... 76
Psychiatrie Complieations and Symptomatology ........................ 77
6. Initial Treatment of Patients Who Present With Liver Disease ........7 9
Introduetion ........................................................................ 79
Initial Therapy ofPatients With Hepatie Failure .............................7 9
Review of Severe, Intermediate, and Mild Hepatie Failure ......... 79
Triaging Patients for Hepatie Transplantation Versus
Initial Medieal Therapy ................................................ 81
Hepatie Transplantation in Wilson's Disease ............................8 5
Indieations for Hepatie Transplantation .............................. 85
Non-indications for Hepatie Transplantation ........................8 6
Anticopper Therapy While Awaiting Transplantation ............ 88
Medieal Therapy for Mild Hepatie Failure .............................. 89
Medieal Therapy for Intermediate Hepatie Failure ...................... 91
A Disaster Resulting From a Failure to Adequately Reevaluate
the Status of a Patient with Intermediate Hepatie Failure
During Medieal Therapy .......................................... 93
Initial Therapy ofPatients With Hepatitis .................................... 94
Initial Therapy ofPatients With Cirrhosis ................................ 95
7. Initial Treatment of Patients Who Present With N eurological
andlor Psychiatrie Disease .....................................................9 7
Introduetion .......................................................................9 7
Neurologieal Worsening ofPatients With Initial
Penicillamine Therapy ...................................................... 98
Reeommended Therapy-Tetrathiomolybdate ............................... 99
Method ofTherapy ..........................................................9 9
Results in an Open Study ................................................. 100
Potential for Aeeessing Tetrathiomolybdate Therapy ................. 101
Alternative Therapies ................ '" ........................................ 102
Zine ........................................................................... 102
Trientine ..................................................................... 102
Contents xiii
8. Maintenance Therapy ......................................................... 10 5
Introduction ...................................................................... 105
Definition of Maintenance Therapy ..................................... 105
Objectives ofMaintenanee Therapy ..................................... 105
Reeommended Maintenanee Therapy-Zine ............................... 106
Method of Therapy ......................................................... 106
Dietary Reeommendations ........................................... 107
Monitoring Zine Therapy ............................................. 108
Zine Side Effeets ...................................................... 109
Overtreatment ......................................................... 109
Results of Zine Therapy in a Large Series of Patients ................ 110
Alternative Maintenanee Therapy ............................................ 114
Trientine ..................................................................... 114
Penieillamine ............................................................... 115
9. Therapy ofthe Presymptomatic, the Pediatric, and
the Pregnant Patient. ......................................................... 117
Therapy for the Presymptomatie Patient. ................................... 117
Definition of Presymptomatie Patient ................................... 117
Usual Methods of Aseertaining Presymptomatie Patients ............ 117
Recommended Therapy for the Presymptomatie Patient-Zine ..... 118
Alternative Therapy for the Presymptomatie Patient ................. 118
Near Disaster and a Disaster Using Penicillamine
Therapy in Initial Therapy ofPresymptomatie Patient. .......... 120
Therapy for the Pediatrie Patient. ............................................ 121
Introduetion ................................................................. 121
Evidenee for Early Disease and Therefore a Rationale for
Early Treatment. ...................................................... 121
Need to A void Overtreatment with Antieopper Agents in
Children with Wilson's Disease ..................................... 122
Reeommended Therapy for the Pediatrie Patient-Zine .............. 122
Alternative Therapy for the Pediatrie Patient ........................... 122
Therapy for the Pregnant Patient ............................................. 123
N eed to Maintain Therapy During Pregnancy .......................... 123
Teratogenieity of Anticopper Therapy .................................. 124
Reeommended Therapy for the Pregnant Patient-Zine ....... " ..... 124
Alternative Therapy for the Pregnant Patient-Trientine ............ 124
10. Risk Factors During Maintenance Therapy and Prognosis .......... 127
Introduetion ...................................................................... 127
A General Risk Faetor-Poor Complianee .................................. 127