In most peroxisomal disorders the nervous system is severely affected which explains the clinical and community burden they represent. This is the first book to focus not only on the mutations causing these inherited illnesses, but also on mechanisms that regulate, suppress or enhance expression of genes and their products (enzymes). Indeed since the success and completion of the Human Genome Project all genes (coding DNA sequences) are known. However, of many, their function, and the role of the gene product has not been determined. An example is X-linked adrenoleukodystrophy, the most frequent peroxisomal disorder. Children are born healthy, but in more than 1 out of 3, demyelination of the brain starts unpredictably and they die in a vegetative state. The gene mutated in most families has been known for 10 years; but the true role of the encoded protein, ALDp, is still speculative; and within the same family, very severe and asymptomatic clinical histories co-exist, unexplained by the mutation.

Peroxisomal disorders constitute a major research front in clinical genetics, paediatrics and cell biology. Since 1983, the metabolic defect in some 20 different peroxisomal disorders has been described. The best known conditions include Zellweger syndrome, rhizomelic chondrodysplasia punctata and X-linked adrenoleukodystrophy and, in the most recent edition of The Metabolic and Molecular Basis Inherited Disease, edited by Scriver and colleagues, more than 100 pages are now devoted to the subject. Progress in our understanding of these conditions, and their diagnosis, results from the application of a variety of laboratory investigations. These include microscopic studies, analysis of metabolites (very long-chain fatty acids, bile acids, and plasmalogens), enzyme studies (peroxisomal beta-oxidation pathway and dihydroxyacetone phosphate acyltransferase), immunodetection of peroxisomal (membrane) proteins and molecular analysis of mutant DNA. In order to encourage a greater awareness in this field and the diagnostic protocols required, an international course was organised in Gent, Belgium, in May 1994, on the clinical and biochemical diagnosis of peroxisomal disorders. A number of international experts in the field who provided intensive hands-on experience over 3.5 days, have now collected their course work and reviews together in this Handbook. The volume is introduced by Sidney Goldfischer, who in 1973 was the first to recognise the absence of peroxisomes in Zellweger syndrome, but whose observations were not fully appreciated for a further decade. This handbook provides the most comprehensive and detailed account of laboratory methods for the diagnosis of peroxisomal disorders. The methods are clearly presented and well illustrated, and should allow laboratories to introduce these methods into their repertoire. Audience: Paediatricians, neurologists, clinical biochemists, pathologists, genetic counsellors, obstetricians, and GPs interested in the recognition, diagnosis and prenatal prevention of peroxisomal disorders.

This book provides an overview of the biology and biochemistry of peroxisomes, and discusses the contribution of these organelles to peroxisomal and neurodegenerative diseases. It begins with a detailed introduction to the biogenesis and metabolic functions of peroxisomes, and highlights their role in oxidative stress and in lipid metabolism such as fatty acid oxidation. The following chapters focus on the molecular and clinical aspects of peroxisomal disorders caused by defects in peroxisomal function. In particular, the biological aspects of peroxisomal biogenesis disorders such as Zellweger syndrome and Heimler syndrome are discussed. This includes their underlying genetic causes as well as the biochemical and metabolic defects associated with the disorders. In addition, several chapters cover recent observations suggesting an association between peroxisomal dysfunction and neurodegenerative diseases such as Alzheimer's, Multiple Sclerosis and other degenerative cerebellar pathologies. The final section of the book discusses important cell and animal models for studying the role of peroxisomes in human diseases and presents current therapeutic strategies for their treatment. This book deals with a highly topical subject that is at the heart of current research, and represents a valuable contribution for all students and researchers who want to understand the complex biology of peroxisomes and their role in human diseases.

Discovered and first isolated in 1966 in C. De Duve's laboratory, peroxisomes - organelles which are present in nearly all eukaryotic cells - are still not fully understood. More than 40 peroxisomal enzymes catalyzing a variety of reactions have been characterized. Moreover, peroxisomes can be regarded as toxicological indicators: several compounds, including hypolipemic drugs, plasticizers or pesticides trigger their proliferation. This proliferation may lead to hepatocarcinogenesis in rodents. Interest in peroxisomes stems not only fromtheir biology, but also because there is a deficiency of peroxisomal functions in several genetic diseases. Some genes involved in inborn errors of peroxisomal function have recently been identified. In this manual, based on a FEBS Advanced Course on peroxisomes, protocols on the following topics are described in detail: Isolation and characterization of peroxisomes by ultracentrifugationand immunoblotting; gene regulation studied by mRNA isolation, hybridizationand DNA cell transfection; use of cell lines as peroxisome proliferator targets; transformation with retrovirus; peroxisomes as toxicological markers; cytochrome P450 induction; drug design and computer analysis of ligand/receptor interaction involved in peroxisomal gene expression.

Discovered and first isolated in 1966 in C. De Duve's laboratory, peroxisomes - organelles which are present in nearly all eukaryotic cells - are still not fully understood. More than 40 peroxisomal enzymes catalyzing a variety of reactions have been characterized. Moreover, peroxisomes can be regarded as toxicological indicators: several compounds, including hypolipemic drugs, plasticizers or pesticides trigger their proliferation. This proliferation may lead to hepatocarcinogenesis in rodents. Interest in peroxisomes stems not only fromtheir biology, but also because there is a deficiency of peroxisomal functions in several genetic diseases. Some genes involved in inborn errors of peroxisomal function have recently been identified. In this manual, based on a FEBS Advanced Course on peroxisomes, protocols on the following topics are described in detail: Isolation and characterization of peroxisomes by ultracentrifugationand immunoblotting; gene regulation studied by mRNA isolation, hybridizationand DNA cell transfection; use of cell lines as peroxisome proliferator targets; transformation with retrovirus; peroxisomes as toxicological markers; cytochrome P450 induction; drug design and computer analysis of ligand/receptor interaction involved in peroxisomal gene expression.

Presents clinical, biochemical, and genetic information concerning those metabolic anomalies grouped under inborn errors of metabolism.