An exploratory matched case-control study to measure blood nutrient levels of adult PKU patients on a protein substitute.

Phenylketonuria (PKU) is an inherited metabolic disorder, where subjects are
born with a genetic deficiency of the hepatic-based enzyme phenylalanine
hydroxylase (PAH) which results in a complete or partial inability to convert
phenylalanine (Phe) into Tyrosine (Tyr). The incidence of PKU varies worldwide
for instance between 1:4000-1:9000 in Turkey, Ireland and Eastern Europe to
1:100,000-1:200,000 in Finland, Japan and Thailand. Due to the genetic deficit,
Phe accumulates in the blood, and there is a shortage of Tyr and its
metabolites. Left untreated, PKU leads to severe mental retardation and
neurological disabilities.
Dietary management of PKU
The main treatment in PKU consists of dietary restriction of Phe often with Tyr
supplementation. Such a diet is strict, and involves limited intake of natural
sources of protein, including but not limited to meat, fish, seafood, dairy,
eggs, nuts and grains. Unsurprisingly, the restrictive nature of the PKU diet
limits dietary intake of several important macronutrients and micronutrients,
resulting in it being naturally poor in e.g.: proteins (and associated
essential amino acids), essential fatty acids (i.e. EPA and DHA), vitamins and
minerals, in particular vitamins D, B6, & B12 as well as selenium, iron,
calcium and zinc.
Nutritional status in PKU subjects
Early diet-treated PKU subjects have reported lower status in several essential
nutrients and micronutrients, increased body mass index (BMI), altered folate
metabolism, plasma lipid peroxidation and other oxidative stresses. Although
much research has been done on the nutritional status in PKU, the adult
population is still largely understudied. This is partly because most screening
procedures were introduced in the 70s and 80s; hence, the *first* groups of
early-diagnosed PKU subjects enter now their mid adulthood. Studying adults
with PKU comes with various challenges adding to the heterogeneity of this
population, e.g. treatment guidelines varied (and still vary) per country and
adherence to the PKU diet and supplementation regimen is one of the key
challenges in adolescence and adulthood. The latter can be a real threat to the
current apparent marginal status of nutrients in PKU as prior studies have
indicated that nutrient levels might be dependent on dietary compliance to
individualized PKU diet and amino acid supplementation regimens. For instance,
most, although not all studies comparing PKU plasma levels of vitamins B6
and/or B12 to reference normal plasma values report endogenous levels in PKU
patients trending towards the lower end of this range. These studies generally
demonstrate an inverse correlation between plasma Phe levels and plasma B6
and/or B12 levels, suggestive for dietary compliance influences. However, even
in cases of adequate dietary compliance to their prescribed diet and amino-acid
regimen, lower levels of DHA have been reported.

The study*s main objective is to measure blood micro- and macronutrient and
amino acid levels in adults with PKU on a protein substitute and compare with
age- and sex-matched non-PKU comparison subjects.

An exploratory matched case-control, multicenter, multi-country study

Not applicable

Participants are asked to complete an online questionnaire once and to complete
a 3-day diet diary. They will need to come to the site once for a study visit
where blood will be drawn via venipuncture. The participants will have to be
come to site in fasted state and should not exercise intensively for 24 hours
before blood sample collection.

The participants do not directly benefit from this study.
There are no risks other than those associated with venipuncture. All other
determinations are non-invasive (dietary assessments, questionnaires,
anthropometric measurements).

The burden is limited as part of the assessments can be performed at home. One
visit is required for the blood sample collection.