The PKU Paradox: A Short History of a Genetic Disease

Chapter 7. Living with PKU

111 CHAPTER SEVEN Living with PKU F F F The management of phenylketonuria through nutritional therapy is inescapably arduous, given the sheer scale of the required reduction in dietary protein, the centrality of food to our cultural identities and social relationships, and the nature of the body’s normal phenylalanine-control system, for which dietary therapy provides only an approximate substitute. We draw here on a series of in-depth interviews with individuals with PKU who attended a major metabolic clinic and on other firsthand accounts of life with PKU, to provide a glimpse into the challenges that the phenylalanine -restricted diet entails. THE PKU DIET: AN OVERVIEW “Diet for Life” When mass screening for PKU began, it was widely assumed that only infants and young children required treatment. As discussed in chapter 5, in the 1960s, most experts believed that the diet could be safely discontinued at about 5 or 6 years of age, when gross brain development was complete. Moreover, given the unpalatable and hard-to-manage medical foods then available, it was generally considered impractical to keep school-age children on the diet. But guidelines later became more conservative, with 112 The PKU Paradox recognition of the need for women to continue the diet at least through reproductive age (since phenylalanine is toxic to the fetus ) and as studies found, first, an association of discontinuation of the diet with cognitive decline and, later, an association with more subtle deficits, such as mood disturbances and declines in attention span, memory, and ability to concentrate.1 The age at which it was considered safe to discontinue the diet crept gradually upward. In time, most clinics in most countries adopted the principle of “diet for life,” a policy endorsed by a consensus conference of the NIH in 2000 and reaffirmed in 2012.2 Over time, too, target ranges for blood phenylalanine levels were generally lowered, and thus the diet became more restrictive. Fifty years after the start of mass heel-stick screening, the lowphe diet remains the foundation of treatment for PKU.3 In the interim, there have been major improvements in the nutritional quality, palatability, and portability of the dietary products. And for patients able to pay out of pocket or whose insurance helps cover the cost, low-protein (low-pro) substitutes for baking ingredients , pasta, rice, and an increasing array of premade food items such as crackers and cookies are now available. But the basis of therapy for PKU remains the same: avoidance of almost all regular sources of protein and consumption of what is variously (and confusingly) called a “protein substitute,” “formula,” or “medical food,” which substitutes for intact protein.4 The dietary regimen is onerous. The protein substitute, which should be consumed in equally divided doses throughout the day, is burdensome to prepare, transport, and keep cold, and it has a bitter taste and unpleasant odor. Even more significant, the foods that either are proscribed or are allowed only in small, measured quantities are ubiquitous. Indeed, the regimen is among the most rigorous medical diets, involving as it does both foods that must be ingested and foods that must be avoided—for a lifetime. Frequent monitoring of blood phenylalanine levels is another feature of life with PKU. To ensure that levels are in the target range, they are monitored weekly or biweekly.5 After infancy, the Living with PKU 113 blood is obtained by lancing the fingertip, a procedure that many adults with PKU recall hating as children. Typical are the memories of a woman who recalls, “I was terrified of blood tests. My family would joke that they could hear me down the hall and out the front steps,” and of a man who reports that, as a small child, “I’d have to be held, like my arm literally held down in order for them to draw blood.”6 In one sense, remarkably little has changed since the 1960s, but in another, the landscape has been radically altered by the shift in treatment guidelines. The challenges of adhering to the PKU diet are greater for older children, adolescents, and adults than for infants and young children, who have never tasted foods that are proscribed and whose parents largely control what they eat. A Utah study found that blood phenylalanine exceeded recommended levels in only 9 percent of 2- to 4-year-olds, but the figure rose to 70...