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.

Fig. 1

Blood phe response to increased phe intake in 2 adults with PKU. Pattern of blood phe concentrations from 2 subjects with biweekly increases in dietary phe intake of 10–20%. Both subjects were adult women with PKU in good control. Reassessment of phe tolerance included daily food records and blood phe monitoring every other day. Values are mean ± SEM.

Fig. 2

Concentration of total AAs and blood urea nitrogen in postprandial plasma with ingestion of the GMP or the AA diet. Plasma was obtained 2.5 h after eating breakfast. Total plasma AA indicates the sum of all AAs measured in plasma. Values are means ± SEM. Total plasma AAs increased and blood urea nitrogen decreased with ingestion of the GMP diet when compared with day 4 of the AA diet. ∗ p < 0.05, significantly different from the AA diet on day 4 (paired t test, pairing on subject). Adapted from Van Calcar et al. [31].