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Organelle Diseases. Clinical Features, Diagnosis and Management.
  1. JOHN H WALTER, Consultant paediatrician

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    Organelle Diseases. Clinical Features, Diagnosis and Management. Edited by D A Applegarth, J E Dimmick, J Hall. (Pp 454; £150 hardback). Chapman and Hall Medical, 1997. ISBN 0-412-54910-7.

    Hands up all of you who know what an organelle is. I asked a colleague, a general practitioner, what he thought one was. “A small thing with long arms”, he replied. That is not exactly right but patients rarely present stating “It’s my organelles doctor”. Knowledge of organelle disease is not really required in general practice. However, at least a rudimentary knowledge of organelle function and the recognition of organelle disorders are becoming increasingly important for paediatricians.

    This book deals primarily with three organelles: lysosomes, peroxisomes, and mitochondria. Some lysosomal diseases, such as the mucopolysaccharidoses, have been well known to paediatricians and pathologists for many years. In contrast to disorders affecting intermediary metabolism, the slow accumulation of substrate may lead to progressive neurological disease often with associated dysmorphic features.

    The peroxisome was first identified in the 1950s by a Swedish PhD student but its significance in human disease was only identified in 1973 when peroxisomes were found to be absent in cerebrohepatorenal (Zellweger) syndrome. We now know that disorders of peroxisomal function are responsible for at least 15 different disorders including X linked ALD, rhizomelic chondrodysplasia punctata, Refsum disease, and hyperoxaluria type 1. Investigations of these and other peroxisomal disorders have led to identification of new biochemical pathways and an understanding of their importance in human metabolism. Mitochondria are primarily responsible for cellular energy production. There has been an enormous increase in our understanding of mitochondrial disease and the rate of acquisition of knowledge is likely to increase. New diseases with strange acronyms, such as NARP, MELAS, MERFF, and MNGIE, have appeared over recent years. Additionally there are now new genetic concepts to understand—for example, maternal inheritance and heteroplasmy.

    Organelle Diseases provides an in depth review of our present knowledge of these three organelles. As stated in the subtitle it deals with clinical features, biochemical and molecular diagnosis, pathogenesis, and management. Professor Charles Scriver, in his foreword, describes this book as linking science with medical practice. Science he describes as an attack on ignorance, and medical practice as a private relationship between practitioner and patient. Certainly there is a great deal of detailed science, and for those with a particular interest in this field it is a delight to see it brought together so well. Medical practice is also covered in some depth. Unfortunately our new knowledge has not yet translated into effective treatment for most organelle disorders. There are important exceptions, such as enzyme replacement treatment in Gaucher disease, but sections on treatment are, as a consequence, somewhat limited.

    This book is a rather curious mixture of detailed science and more basic clinical practice. For example, there is a section on the stoichiometry of ATP synthesis and, in contrast, a chapter on how to take a family history. However, the format works well and I would certainly strongly recommend it to clinicians, biochemists, and anyone with an interest in biochemical genetics. Any book that has its text positioned between a foreword by Professor Charles Scriver and a postscript by Professor Victor McKusick is likely to have a lot going for it!

    What is an organelle? Fortunately Organelle Diseases contains an excellent glossary and provides the following definition “A membrane bound intracellular cytoplasmic structure having specialised functions”. Now you know.