Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management

Abstract

The disciplines of molecular biology and haematology have been closely intertwined. Many of the initial insights into the general principles of protein structure and function were obtained during the course of work on the haemoglobin molecule performed by Perutz, Pauling and others. The subsequent realization that just a single aminoacid substitution in the β-chain of haemoglobin is responsible for sickle-cell disease, with its wide range of clinical manifestations, laid a basis for the revolution in understanding of human disease at the molecular level. Since then, research work on the organization and regulation of expression of the globin genes has continued to lead the way in providing understanding of wider principles of eukaryotic gene expression and its control. Disorders of Hemoglobin provides a comprehensive review of both the scientific and the clinical aspects of human erythropoiesis and its disorders. It offers a collection of well written chapters by leading international investigators, many of whom are able to refer to the contribution their own research work has made to the field. The chapters are grouped in eight sections covering the basic science of haemoglobin and red-cell physiology and the related clinical disorders—the thalassaemias, sickle-cell disease and other haemoglobinopathies. The chapters are detailed and succeed in providing state-of-the-art summaries of their topic area. All are extensively referenced and enable the reader to appreciate which original scientific papers have led to current models of thought. Furthermore, especially in the first basic science section, many of the chapters include detail of the history of the understanding of their topic areas, illustrating well the development of thinking over time on particular aspects of the field. A particular highlight is the chapter by Max Perutz on the molecular structure and function of haemoglobin. The sections focusing on the thalassaemias, sickle-cell disease, other sickle haemoglobinopathies and the rarer disorders of haemoglobin function and stability are again comprehensive, detailed and well written. These diseases are discussed very much from a scientific angle and the chapters emphasize molecular pathophysiology, together with physical chemistry and rheology where appropriate. The chapters on clinical management are strong and there is generally clear reference to the evidence base provided by experimental and clinical trial data. Of particular interest are the chapters summarizing the extensive role of malaria in defining the epidemiology of human red-cell disorders and the chapters updating the current thinking on treatment strategies, including iron chelation, hydroxyurea therapy, bone marrow transplantation and gene therapy. In summary, this is a fine and accessible text that can be recommended for students, scientists and clinicians who seek detailed reviews of red-cell disorders and their clinical management. For MRCPath haematology candidates who are daunted by the length of the whole book I would recommend selective reading of the chapters on clinical management (sections 2-4) and laboratory diagnosis (section 6). These chapters are as good as I have found anywhere. This text is not well suited to those preparing for MB or MRCP examinations, who can gain the information they require from much shorter works.