Nutritional Management of Phenylketonuria

Abstract

Phenylketonuria (PKU) is caused by deficient activity of the enzyme phenylalanine hydroxylase, needed to convert the essential amino acid (AA) phenylalanine (phe) to tyrosine. In order to prevent neurological damage, lifelong adherence to a low-phe diet that is restricted in natural foods and requires ingestion of a phe-free AA formula to meet protein needs is required. The goal of nutritional management for those with PKU is to maintain plasma phe concentrations that support optimal growth, development, and mental functioning while providing a nutritionally complete diet. This paper reviews developing a lifelong dietary prescription for those with PKU, outcomes of nutritional management, compliance with the low-phe diet across the life cycle, and new options for nutritional management. An individualized dietary prescription is needed to meet nutrient requirements, and the adequacy of phe intake is monitored with assessment of blood phe levels. Elevated phe concentrations may occur due to illness, excessive or inadequate phe intake, or inadequate intake of AA formula. Although normal growth and development occurs with adherence to the low-phe diet, it is important to monitor vitamin, mineral and essential fatty acid status, especially in those who do not consume sufficient AA formula. Given the growing population of adults with PKU, further research is needed to understand the risks for developing osteoporosis and cardiovascular disease. There are promising new options to liberalize the diet and improve metabolic control such as tetrahydrobiopterin therapy or supplementation with large neutral AAs. Moreover, foods made with glycomacropeptide, an intact protein that contains minimal phe, improves the PKU diet by offering a palatable alternative to AA formula. In summary, continued efforts are needed to overcome the biggest challenge to living with PKU – lifelong adherence to the low-phe diet.

Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

“…The primary therapy for PKU is life-long adherence to a diet that limits phe intake to the minimum amount needed to support growth and protein turnover (40). The low-phe PKU diet requires extensive restriction of foods containing natural protein (often only 5-10 g protein per day are allowed) and supplementation with amino acids (AA), usually in the form of a formula, to achieve adequate intake of nitrogen, indispensable AA, and micronutrients (31). Compliance with the low-phe diet is often poor after 10 yr of age, despite the detrimental neuropsychological consequences of hyperphenylalanemia (23,57).…”

Learning, the Sole Explanation of Human Behavior: Review of The Marvelous Learning Animal: What Makes Human Nature Unique

“…They also found that the non-defective version of the gene produces enzymes necessary for metabolizing phenylalanine, an amino acid toxic to neurons at high doses. A diet with limited phenylalanine, supplemental amino acids, and other nutrients prevents phenylalanine from accumulating and killing young children (Macleod & Ney, 2010), even though the genetic defect remains.…”

Current situation and prospects of newborn screening and treatment for Phenylketonuria in China - compared with the current situation in the United States, UK and Japan

“…The acknowledged mainstream treatment for PKU patients is a strict Phe-restricted diet supplemented by a medical formula containing amino acids and other nutrients (63). However, the treatment for PKU is variable among different countries.…”