Abstract
This book belongs to the ‘Oxford Monographs on Medical Genetics’ series, and the back cover claims that it ‘establishes an innovative pathway approach and provides a new authority on this family of diseases’. The book is divided into three sections: newborn screening, pathways and therapeutic approaches.
The newborn screening chapter did not provide a promising start. It contains a brief (two pages) methods section that features terminology that is at times confusing or incorrect (e.g. galactose-1-phosphate uridyltransferase enzyme activity screening is described as using fluoroimmunoassay). Furthermore, techniques are described that are not relevant for newborn screening or detection of inborn errors of metabolism (e.g. electrophoresis and isoelectric focusing). The six inborn errors screened for by the UK expanded panel are outlined, although it is not made clear that homocystinuria screening is only for the pyridoxine non-responsive form. These descriptions are potentially useful but again let down by errors (two examples: detectable argininosuccinic acid is described as pathognomonic for arginase deficiency, and urine homocysteine is recommended as a confirmatory test for classical homocystinuria).
The pathways section includes 10 chapters. For a book that claims to provide a ‘new authority’ on inborn errors of metabolism, it is perhaps surprising that several groups of diseases were not covered in this section (e.g. disorders affecting lysosomal storage, purine and pyrimidine metabolism, metabolism by peroxisomes and several of the amino acid disorders). Positive aspects of this section are that the pathways covered are well described and that comprehensive and up-to-date descriptions of the inherited conditions affecting them are provided. Where present, the diagrams were a helpful aid to visualizing the pathways being discussed, but some chapters could have benefitted from extra diagrams, e.g. the folate and cobalamin pathways. Importantly, the primary literature was comprehensively cited at the end of each chapter which would make this book useful as a starting point for further reading. The promised ‘innovative pathway approach’ seeks to demonstrate the wider effects of an inborn error affecting a particular pathway and this was successfully achieved, especially in the urea cycle and branched chain amino acid chapters. Mechanisms of pathogenesis were also covered well in this section with data from animal models often used to try and provide explanations for clinical observations. However, the descriptions of biochemical abnormalities were for the most part qualitative in nature, when a description of the expected magnitude of deviations from reference ranges would have been more useful.
The therapeutic approaches section contained chapters on transplantation, gene replacement, enzyme replacement, substrate reduction and chaperone therapies. The last three of these are primarily targeted to lysosomal storage disorders yet, strangely, these conditions are not covered in the pathways section of the book. On the other hand, some of the material in this section was unnecessarily duplicated elsewhere within the book: for example substrate reduction therapy has its own chapter yet is also covered in the both the chaperone therapy and enzyme replacement therapy chapters. This section may not be of direct relevance for laboratory-based scientists and medics, but I found that it was easy to follow and informative about the current state of play for treatments that are available or currently in development or clinical trials.
I do not feel that I could recommend this book as preparation for FRCPath examinations, as many conditions are not covered and some of the chapters go into depth beyond what would be required. However, as an up-to-date summary of the specific areas covered, this book would be a useful reference and a starting point for further reading.