Mitochondrial Disorders: From Pathophysiology to Acquired Defects

314 Pages·2002·7.3 MB·English

by  Pr Claude Desnuelle

Mitochondrial Disorders
from pathophysiology to acquired defects
Springer-Verlag France S.A.R.L
c.
Desnuelle, S. DiMauro
Mitochondrial Disorders
from pathophysiology
to acquired defects
, Springer
Pr Claude Desnuelle, Dr Salvatore DiMauro,
Federation des Maladies Columbia University College
N euromusculaires, of Physicians and Surgeons
Hopital de l' Archet, CHU de Nice, NewYork,
France United States
ISBN 978-2-8178-0931-1 ISBN 978-2-8178-0929-8 (eBook)
DOI 10.1007/978-2-8178-0929-8
© Springer-Verlag France 2002
Softcover reprint of the hardcover 1st edition 2002
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Cover design: Nadia OUDDANE
Cover illustration: © 1995, Massaehusetts Medieal Soeiety. All rights reserved. In The New
0/
England Journal Medicine, Journal Watch News Letters, & AIDS Clinical Care, v. 333, p. 1051,
10/19/1995, Barnard, Miehelson, «A morphologie Question».
list of authors
Dr Joaquin Arenas, Hospital Universitario 12 de Octobre, Centro de Investigaciones, Madrid,
Spain.
Dr M. Flint Beal, Department ofNeurology and Neuroscience, New York Presbyterian Hospital,
Weil Medical College of Cornell University, New York, United States.
Dr Olivier Benveniste, Service de Medecine Interne 1, Höpital Pitie-Salpetriere, Paris, France.
Pr Laurence Bindoff, Institute of Neurology, University of Bergen, Haukeland University
Hospital, Bergen, Norway.
Dr Kees Brinkman, Department of Internal Medicine, Onze Lieve Vrouwe Gasthuls Hospital,
Amsterdam, Netherland.
Dr Menotti Calvani, Head Scientific Department, Sigma-Tau S.p.A., Pomezia, Italy.
Dr Brigitte Chabrol, Unite de Medecine Infantile, Höpital Enfants, CHU La Timone, Marseille,
France.
Dr Yann-Erick Claessens, Service de Reanimation Polyvalente, Höpital Cochin, Paris, France.
Dr Darryl De Vivo, Department ofNeurology, Columbia University, College ofPhysicians and
Surgeons, New York, United States.
Pr Claude Desnuelle, Service des Maladies Neuromusculaires, Höpital de I'Archet, CHU de
Nice, Nice, France.
Pr Stefano Di Donato, Instituto Neurologicalo, Dipartimento di Biochimica e Biologia
Molecolare, Bari, Italy.
Dr Salvatore DiMauro, Columbia University College of Physicians and Surgeons, New York,
Uni ted States.
Dr Bernard Fromenty, INSERM U481, Höpital Beaujon, Clichy, France.
Dr Anne Lombes, INSERM U523, Institut de Myologie, Höpital Pitie-Salpetriere, Paris, France.
Dr Anders Oldfors, Department of Pathology, Sahlgrenska University Hospital, Gothenburg,
Sweden.
Dr Veronique Paquis, Laboratoire de Genetique, Höpital de I'Archet, Nice, France.
Dr Guiseppe Paradies, Dipartimento di Biochimica e Biologia Molecolare, Bari, Italy.
Dr Gianfranco Peluso, Centro Nazionale Ricerche, Instituto di Biochimica delle Proteine ed
Enzimologia, Napoli, Italy.
Dr Norma Beatriz Romero, Institut de Myologie, Höpital Pitie-Salpetriere, Paris, France.
Dr Pierre Rustin, INSERM U393, Höpital Necker-Enfants Malades, Paris, France.
Dr Vincent Sapin, Faculte de Medecine, Clermont-Ferrand, France.
Pr Georges Serratrice, Service des Maladies Neuromusculaires, CHU La Timone, Marseille,
France.
Pr Serenella Servidei, Institute of Neurology, Catolic University, Roma, Italy.
Dr Marc Tardieu, Service de Neurologie pediatrique, Höpital Bicetre, Le Kremlin-Bicetre, France.
Dr Douglas Turnbull, Department of Neurology, University of Newcastle Upon Tyne, United
Kingdom.
Pr Bernard Vialettes, Service Endocrinologie-Nutrition, Höpital Sainte-Marguerite, Marseille,
France.
Table of contents
Introduction
G. Serratrice ................................................................................................... .
Mitochondrial Biology
The Mitochondrial Machinery
S. Di Donato.................................................................................................... 5
Mitochondria in Neurodegeneration
M.F. Beal ..................................... ................................................................... 17
Apoptosis and Oxidative Stress in Mitochondrial Disorders
S. Servidei, S. Di Giovanni, A. Broccolini, A. D'Amico, M. Mirabella and
G. Silvestri ...................................................................................................... 37
Mitochondria and Ageing
D.M. Turnbull and M.l. Barron ........................................................................ 47
Cardiac Mitochondrial Dysfunction in Aging and in Ischemial Reperfusion.
Role of Oxygen Free radicals and Cardiolipin
G. Paradies, G. Petrosillo and F.M. Ruggiero ................................................ 59
Deregulation of Mitochondrial Apoptosis in Cancer
G. Peluso, O. Petillo, S. Margarucci, A. Calarco and M. Calvani ........................ 71
latrogenic Mitochondrial Diseases
Drug induced Hepatotoxicity and Mitochondrial Dysfunction
B. Fromenty, C. Maisonneuve, R. Note, A. Berson and D. Pessayre........... ..... 91
The Carnitine System Involvement in Mitochondrial Pharmacologic
Sensitivity
M. Calvani, P. Benatti, R. Nicolai and E. Reda ................................................ 107
Mitochondrial Toxicity of Anti-Retroviral Drugs
K. Brinkman .................................................................................................... 131
Mitochondrial Damage in HIV Patients treated with Highly Active Anti
retroviral Therapy
A. Lombes, C. Barthe!emy, C. Jardel, E. Teicher, T. Maisonobe and D. Vittecoq. 141
Hyperlactatemia and HIV-infected Patients with Nucleoside Analog
Reverse- transcriptase Inhibitors Treatment: the Clermont HIV Cohort Study
V. Sapin, G. Marceau, C. Jacomet, C. Boniol, L. Cormerai, H. Laurichesse,
B. Dastugue, J. Bey taut and O. Boespflug-Tanguy.......................................... 153
Table of contents III
Severe LacticAcidosis and Multiple Organ Failure in HIV Patients treated
with Nucleoside Analogues reverse Transcriptase Inhibitors: a Pilot
Study of Treatment with L-Carnitine
Y.E. Claessens and A. Cariou ........................................................................ 161
Mitochondrial Dysfunction in Perinatal Exposure to Antiretroviral
Nucleoside Analogues
M Tardieu, P. Rustin, MJ. Mayaux and 5. Blanche........................................ 173
Mitochondrial Myopathy in Non-Infected New-Born from HIV-1 Mothers
treated with Antiretroviral Drugs
NB. Romero, C. Lacroix and J.F. Pellissier........................................................ 183
Mitochondrial Medicine
Neurologieal Features of Genetie and Acquired Metabolie Mitochondrial
Defects
C. Desnuelle, C. Richelme and V. Paquis-Flucklinger........ .............................. 193
Clinieal Heterogeneity associated to Dysfunction of Mitochondrial DNA:
the exemple of the 3243 "MELAS" Mutation
V. Paquis-Flucklinger ...................................................................................... 211
Inborn and Acquired Mitochondrial Leucodystrophy
B. Chabrol and C. Raybaud ............................................................................ 221
Mitochondrial Dysfunction, Epilepsy, and Antiepileptie drugs
D.C. Oe Vivo, D. Nordli and 5. DiMauro.......................................................... 231
Friedreieh Ataxia as an Example of the Dual Genome Control of Mito
chondrial Function
P. Rustin, V. Geromel, N Darin, A. Munnich and A. Rötig .............................. 247
How wide are Mitochondria involved in Exercise Intolerance?
J. Arenas, Y. Campos, MA. Martin, 5. DiMauro and A.L. Andreu.................. 255
Mitochondrial Defects in Myositis and Inclusion Body Myopathies
A. Oldfors ........ ................................................................................................ 265
Mitochondrial Dysfunction and the Gastrointestinal System
L. Bindoff ........................................................................................................ 275
Mitochondrial Diabetes: Clinieal Specificity and Diagnosis
B. Vialettes and H. Narbonne .............................................. ............................ 287
Mitochondrial Featuring in Kidney Disorders and Myelodysplastie Syndromes
O. Benveniste and 5. Herson .......................................................................... 295
Treatment
Treatment of Mitochondrial Diseases
5. DiMauro ...................................................................................................... 307
Introduction
G. SERRATRICE
This book is new and original. For some decades mitochondriopathies have
been extensively studied: morphology, biochemistry, genetics. However these
studies mainly concerned encephalopathies and myopathies related to mito
chondrial disorders.
In this book the field of mitochondrial cytopathies is largely extended to
"Mitochondrial Medicine". Very new data are gathered. A new step is jumped.
Many medical specialities are concerned.
Part I is devoted to mitochondrial biology: the mitochondrial machinery,
the dysfunction of mitochondrial in elderly: cell decline, deleterious effects of
oxidative stress in ageing, especially dysfunction of cardiac mitochondria, as
well mitochondrial involvement in neurodegeneration.
An attractive chapter concerns the implication of apoptosis, the programmed
cell death, linked to cytochrome oxidase defect.
Iatrogenic mitochondrial diseases are studied in Part II either due to a sen
sitivity to some drug or especially induced by antiretroviral drugs. Several drugs
lead to a mitochondrial toxicity: antiepileptic treatment, anticancer drugs.
Mitochondrial damage involving mainly the mitochondrial DNA is frequent
in patients treated for several years by antiretroviral drugs, with absolute deple
tion of mitochondrial DNA. Some patients with severe lactic acidosis and mul
tiple organ failures may be improved by carnitine. Special problemes arise in
newborn and in perinatal exposure to antiretroviral drugs. In case of treated
mother a mitochondrial disease could occur in non infested newborn.
Part III covers mitochondrial medicine. Many organs are concerned: central
nervous system in general, by the way, it is important to carefully choose an
antiepileptic during the treatment of mitochondrial encephalopathies with sei
zures. Friedreich ataxia, leucoencephalopathy in children. Gther groups are
mitochondrial diabetes, heart involvement, kidney disorders, haematologic syn
dromes, mitochondrial dysfunction in inflammatory diseases, in particular in
inflammatory myopathies, relation between mitochondrias and the gastroen
terological system. Another aspect is exercise intolerance related to mito
chondrial dysfunction in young people.
Part IV gathers the possibilities of treatment. Palliative therapy is usefull in
mitochondrial medicine: drugs to alleviate symptoms, cardiac, gastrointestinal,
2 G. Serratrice
endocrine. More specific are pharmacological therapies: vitamine C, vitamine K
or B. Coenzyme Q 10 as carnitine could have beneficial effects in some patients.
Of course gene therapy may be the future treatment. Ir has been applied to
human cells in culture aiming to convert mutant genes into normal nuclear
genes. Another approach is to cause a shift in the proportion of mutant and
wild type of mitochondrial DNA, using peptides nucleic acides. The use of
satellite cells is limited to myopathies.
This book on the mitochondrial medicine is a comprehensive review of the
recent advances in the field of many diseases. The volume will be of interest
to clinicians an researchers interested in various aspects of mitochondrial dys
functions. This book, containing the latest informations presented by outs
tanding clinicians and researchers not only will serve to disseminate the current
knowledge of the mitochondriopathies to the clinicians in internal medicine
and several specialities but will also provide the basis for further clinical and
laboratory research studies on mitochondrial medicine.