Book Reviews

Hemochromatosis: Genetics, Pathophysiology, Diagnosis, and Treatment by James C Barton, Corwin Q Edwards, editors. Book Review by Vincent J Felitti, MD

Medical futurists have predicted that hemochromatosis will be the cholesterol of the 21st century in terms of public notice. Discovery of the HFE gene has now shown that one in 250 Americans has the homozygous genotype for hemochromatosis--the most common genetic disease in the country despite what most physicians currently believe. The patient panel of most Permanente primary care physicians includes about ten cases of hemochromatosis.

Almost no current cases of hemochromatosis are diagnosed. Of course, many affected patients are presymptomatic because they are young enough still to be in the process of accumulating toxic levels of iron. In other patients (for reasons not yet understood), complete penetrance never manifests. But many patients with hemochromatosis are symptomatic, manifesting the myriad signs and symptoms that most physicians still do not appreciate. Cardiomegaly, fatigue, arthralgias, episodic diarrhea, hypothyroidism, arrhythmias, impotence, diabetes, and joint replacement are among the numerous presentations of iron overload. Each of these conditions has other, more common explanations; these multiple signs and symptoms perpetuate the traditional belief that hemochromatosis can be considered--indeed, dismissed--as a rare disease.

Hemochromatosis is important--and is an ideal subject for preventive medicine--because of its prevalence, its easy early diagnosis, and the probability that early diagnosis and treatment will totally prevent every manifestation. Largely because of these factors, the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) have selected hemochromatosis as the prototype disease to be featured in a nationwide program to help practitioners move into the era of genetic disorders.

James Barton and Corwin Edwards are two American physicians with enormous clinical experience in hemochromatosis who have brought together 100 of the world's experts on iron overload to create a major monograph about hemochromatosis that will dominate the field for years to come. Their book, Hemochromatosis, is clearly written, evenly edited, and well made. It is also timely because it is the only monograph available in a field that is rapidly expanding; the other two books on this disorder were published in 1935¹ and 1964,² respectively.

The first section of Hemochromatosis discusses the history of this common hereditary disorder, which is the most common cause of all diseases of iron overload. The discussion of the genetics of hemochromatosis makes the important point that iron overload is the essence of the disease; and that the mechanism by which that iron overload is accomplished--genetic or not--is not the essential issue for patients. We learn that normal genetic analysis is therefore not at all reassuring when evidence shows the presence or likely development of iron overload.

Subsequent chapters discuss available diagnostic techniques, which range from serum iron saturation through tissue biopsy to magnetic resonance imaging (MRI); the limits of genetic analysis are also made clear. The chapters on clinical presentations remind us that Sir William Osler's dictum "Know syphilis and you know all of medicine" could easily be rewritten as "Know hemochromatosis and you know much of medicine." This view is quite different from what many of us vaguely recall about "bronze diabetes with cirrhosis," that end-stage triad in which delayed diagnosis causes the benefits of therapy to be lost.

The book describes various aspects of treatment, ranging from the standard of phlebotomy through the occasional need for the infused chelating agent, deferoxamine mesylate (Desferal, Ciba-Geneva Pharmaceuticals, Summit, NJ), to the need (which we hope is rare) for liver transplantation. The book also discusses ways in which infection and malignancy are caused by diseases of iron overload (in particular, unusual types of septicemia and hepatoma). Subsequent chapters discuss screening, the combination of hemochromatosis with other disorders (eg, thalassemia trait, alcoholism), and hemochromatosis in animals. Screening is of particular importance because it provides the greatest opportunity for therapy. Closing chapters discuss general problems associated with screening for genetic diseases and transfusing blood from hemochromatosis patients. Changes in blood bank regulations may soon allow this blood to be used within Kaiser Permanente (KP).

This skillful organization of knowledge into a highly readable monograph is a pleasure to use. All KP medical libraries will want this book. I suspect that many Permanente physicians will refer to Hemochromatosis as they start recognizing the possibility--perhaps even the likelihood--that some of their patients have hemochromatosis that is undiagnosed. To the degree that this diagnosis is facilitated, patients gain the opportunity for effective treatment of this disease.

$215 ISBN 0521593808 Cambridge: Cambridge University Press, 2000.

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