Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH4)

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 AE 476 mg to 2131 AE 1084 mg (P ¼ 0.006) under BH 4 while maintaining good metabolic control (Phe concentration in dried blood 283 AE 145 mM vs. 304 AE 136 mM, P ¼ 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 ¼ 0.016), iron (P ¼ 0.002), calcium (P ¼ 0.017), iodine (P ¼ 0.005) and zinc (P ¼ 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.

PKU patients on a relaxed diet may be at risk for micronutrient deficiencies

“…15 However, this seems not to be true for patients with a high Phe tolerance: relaxing the diet because of increased Phe tolerance by addition of BH 4 led to decreased consumption of fruits and vegetables and consequently vitamin C supply. 10 Of concern, the intake of calcium and vitamin D is far below the recommendations, confirming earlier studies. 16 In a subgroup of 12 patients for whom plasma 25-OH-vitamin D was available, 9 showed concentrations at or below the lower limit of normal (mean ¼ 19 ng/ml; range ¼ 7.9-29.7), underlining the insufficient vitamin D supply.…”

“…It can be expected that the number of PKU patients on a relaxed diet without AAM supplement will increase in the coming years because of the relatively new and successful cofactor therapy with tetrahydrobiopterin (BH 4 ) in patients with BH 4 -sensitive PKU. 9,10 These patients are at risk of continuous micronutrient deficiencies with all known long-term consequences. [11][12][13] In general, basic eating habits develop during early childhood and remain stable throughout life.…”

“…14 In a previous study, we could show that patients who could relax their diet because of BH 4 sensitivity had difficulties to consume adequate amounts of meat and dairy products. 10 In this respect, ending the AAM supplementation in any PKU patient needs careful consideration, dedicated dietary counseling and close follow-up. It might be useful to provide these PKU patients with a specialized micronutrient mixture to bridge the time until their eating habits normalize toward sufficient micronutrient supply from natural sources.…”

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients

“…3,54 On the other hand, few other studies have shown that phenylketonuria patients following a strict diet supplemented with phenylalanine-free amino acid formulae were not at risk of developing deficiencies in these micronutients. 55,56 More studies are required to clarify these conflicting results.…”

Stress and quality of life in parents of children with phenylketonuria

“…Phenylketonuria (PKU) is one of the most common congenital metabolic abnormalities caused by the mutation in the gene that codes for the phenylalanine hydroxylase enzyme (PAH; Gunduz et al, ). In the absence or disruption of the enzyme performance, impaired phenylalanine to tyrosine conversion, phenylalanine accumulation in the blood and tissues, and deficiency of tyrosine occurs (Thiele et al, ). The prevalence of PKU in Western and Northern European and Caucasian infants is about 1 in 10,000 (Fidika, Salewski, & Goldbeck, ).…”