Nutritional status of patients with phenylketonuria in Japan

Abstract

Accumulating evidence suggests that hyperphenylalaninemia in phenylketonuria (PKU) can cause neuropsychological and psychosocial problems in diet-off adult patients, and that such symptoms improve after resumption of phenylalanine-restricted diet, indicating the need for lifetime low-phenylalanine diet. While limiting protein intake, dietary therapy should provide adequate daily intake of energy, carbohydrates, fat, vitamins, and microelements. We evaluated nutrient balance in 14 patients with classical PKU aged 4-38 years. Approximately 80-85% of the recommended dietary allowance (RDA) of protein in Japanese was supplied through phenylalanine-free (Phe-free) milk and Phe-free amino acid substitutes. Nutritional evaluation showed that the calorie and protein intakes were equivalent to the RDA. Phenylalanine intake was 9.8 ± 2.2 mg/kg of body weight/day, which maintained normal blood phenylalanine concentration by the 80% Phe-free protein rule. The protein, fat, and carbohydrate ratio was 9.5:23.9:66.6% with relative carbohydrate excess. Phe-free milk and amino acid substitutes provided 33.7% of carbohydrate, 82.1% of protein, and 66.7% of fat intake in all. Selenium and biotin intakes were 25.0% and 18.1% of the RDA and adequate intake (AI) for Japanese, respectively; both were not included in Phe-free milk. PKU patients showed low serum selenium, low urinary biotin, and high urinary 3-hydroxyisovaleric acid in this study. The intakes of magnesium, zinc, and iodine were low (71.5%, 79.5%, and 71.0% of the RDA, respectively) and that of phosphorus was 79.7% of the AI, although they were supplemented in Phe-free milk. PKU patients depend on Phe-free milk and substitutes for daily requirement of microelements and vitamins as well as protein and fat. Development of low-protein food makes it possible to achieve the aimed phenylalanine blood level, but this lowers the intake of microelements and vitamins from natural foods. The dietary habits vary continuously with age and environment in PKU patients. We recommend the addition of selenium and biotin to Phe-free milk in Japan and the need to review the composition of microelements and vitamins in A-1 and MP-11 preparations.

Keywords: Biotin; Iodine; Magnesium; Microelement; Nutrition; Phenylalanine hydroxylase; Phenylketonuria; Phosphorus; Selenium; Vitamin; Zinc.

Fig. 1

Blood phenylalanine concentration in PKU patients where Phe-free milk and amino acid substitutes account for 80–85% of protein intake.

Fig. 2

Status of calorie intake, protein intake, and calorie balance for protein, fat, and carbohydrates in the Phe-free milk group and A-1/MP-11 group. (A) Ratio of calorie intake to age-and gender-specific RDA. (B) Average phenylalanine intake per body weight per day. (C) Calorie balance according to protein, fat, and carbohydrates. Data are mean ± SD. P values by Student's t-test.

Fig. 3

Intake of microelements in PKU patients relative to age-and gender-specific RDA or AI in the Phe-free milk and A-1/MP-11 groups. Data are mean ± SD. P values by Student's t-test.

Fig. 4

Vitamin intake in PKU patients relative to age-and gender-specific RDA or AI in the Phe-free milk and A-1/MP-11 groups. Data are mean ± SD. P values by Student's t-test.

Fig. 5

Percentages of intake of microelements and vitamins from natural foods and Phe-free milk, A-1, and MP-11 relative to age-and gender-specific RDA or AI. Blue (Lower) bars: percentage intake from natural foods relative to the RDA or AI. Orange (Upper) bars: percentage of intake from Phe-free milk, A-1, and MP-11 relative to the RDA or AI. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 6

Estimated changes in energy, protein, and microelements intakes by the simulation to replace 20% protein in the Phe-free milk with MP-11in Phe-free milk group and A-1/MP-11 group. In Phe-free milk group, the source of protein intake was adjusted to be 20% from natural protein, 20% from MP-11, and 60% from Phe-free milk. In the A-1/MP-11 group, the source of protein intake was adjusted to be 20% from natural protein, 40% from MP-11, and 40% from Phe-free milk. T Blue (left side) bars: before estimation, orange (right side) bar: after estimation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 7

The distribution of serum selenium, serum free and total biotin, urinary free biotin, and urinary 3-hydroxyisovaleric acid levels in classical PKU patients. Data are mean ± SD. n: number of examined patients. Dark box: reference values.