Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH(4))

Abstract

Background: Since 2008 patients with BH(4)-sensitive phenylketonuria can be treated with sapropterin dihydrochloride (Kuvan®) in addition to the classic phenylalanine (Phe) restricted diet. The aim of this study was to evaluate the nutritional changes and micronutrient supply in patients with phenylketonuria (PKU) under therapy with tetrahydrobiopterin (BH(4)).

Subjects and methods: 19 children with PKU (4-18 years) and potential BH(4)-sensitivity were included, 14 completed the study protocol. Dried blood Phe concentrations as well as detailed dietary records were obtained throughout the study at preassigned study days.

Results: Eight patients could increase their Phe tolerance from 629 ± 476 mg to 2131 ± 1084 mg (P = 0.006) under BH(4) while maintaining good metabolic control (Phe concentration in dried blood 283 ± 145 μM vs. 304 ± 136 μM, P = 1.0), therefore proving to be BH(4)-sensitive. They decreased their consumption of special low protein products and fruit while increasing their consumption of high protein foods such as processed meat, milk and dairy products. Intake of vitamin D (P = 0.016), iron (P = 0.002), calcium (P = 0.017), iodine (P = 0.005) and zinc (P = 0.046) significantly declined during BH(4) treatment while no differences in energy and macronutrient supply occurred.

Conclusion: BH(4)-sensitive patients showed good metabolic control under markedly increased Phe consumption. However, the insufficient supply of some micronutrients needs consideration. Long-term multicenter settings with higher sample sizes are necessary to investigate the changes of nutrient intake under BH(4) therapy to further evaluate potential risks of malnutrition. Supplementation may become necessary.

Fig. 1

Study design of BH₄-intervention trial in PKU patients. BH ₄ tetrahydrobiopterin, PAH phenylalanine hydroxylase, Phe phenylalanine, DB dried blood, DR dietary record

Fig. 2

Food consumption of BH₄-sensitive patients on classical dietary treatment (left bar) compared to BH₄ therapy during follow-up (right bar). Shown are the shares of food groups (%) of total food consumption (*significant difference between period 1 and 4: bread (P = 0.022), dairy products (P = 0.002); potatoes, pasta and rice (P = 0.021), food of animal origin (meat, processed meat, fish, egg, P = 0.016); special low protein products (P = 0.009))

Fig. 3

(a–b) Protein and micronutrient supply of BH₄-sensitive patients (n = 7) under Phe restricted diet (upper bar) and under BH₄ therapy during follow-up (middle bar) compared to age-matched healthy German children (lower bar) as percent of DACH-RDA. Shown are the shares of food and amino acid mixture (AAM) of the total nutrient supply. The vitamin C content of Kuvan® was included into the calculation. Under the Phe restricted diet all these patients took an amino acid mixture while under BH₄ therapy only two patients took some (* significant differences in total micronutrient supply in BH ₄ -sensitive patients under Phe restricted diet compared to BH ₄ therapy: P _{vitamin D} = 0.016; P _iron = 0.002; P _calcium = 0.017; P _iodine = 0.005, P _zinc = 0.046)