Abstract

Metabolic Unit, Reference Center for Metabolic Diseases, CHULN-HSM
Summary:
Phenylketonuria (PKU) dietary management involving protein restriction remains an effective treatment of the disease preventing neurocognitive compromise. The goal is to limit the accumulation of toxic amounts of phenylalanine (Phe), an essential amino acid. A combination of natural protein and Phe-free, tyrosine rich formulas are needed to provide adequate amounts of tyrosine for growth and neurotransmitter synthesis, with just enough Phe for anabolism. Although, long term protein restricted diets can lead to suboptimal bonne health outcomes, potentially leading to growth failure and fractures.
Authors intend to perform a retrospective study to evaluate the bonne health of PKU patients followed at Lisbon Reference Center for Inborn Errors of Metabolism, CHULN, concerning bonne mineralization and fracture risk.
The clinical charts of all PKU patients summitted to dual energy X-ray absorptiometry (DEXA) evaluation will be reviewed regarding:
1. Mineral bonne density by DEXA, according to patient´s age and gender;
2. Demographic data regarding gender, age, puberty status, dietary compliance, type, duration and frequency of exercise and fracture occurrence;
3. Energy, protein (natural and synthetic), calcium, phosphorus, magnesium and vitamin D daily intake in the patient´s diet and pharmacological supplementation, previous to DEXA evaluation;
4. Plasma biochemical evaluation of calcium, phosphorus, magnesium, alkaline phosphatase, vitamin D, parathyroid hormone (PTH), median Phe levels and urinary calcium excretion, previous to DEXA evaluation;
5. Anthropometric data (weight, height and body mass index), according to World Health Organization (WHO) percentiles and z-scores to gender and age, at the time of DEXA evaluation;
6. Calcium content of amino acid mixtures, glycomacropeptide (GMP) intake and Kuvan supplementation will also be addressed.

There is no animal testing.

STATE OF THE ART

Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency in l-phenylalanine-4-hydroxylase (PAH) activity, leading to elevated levels of Phe in body fluids. Worldwide implementation of newborn screening to detect PKU has enabled early diagnosis and treatment, preventing severe mental retardation of PKU patients. PKU treatment mainly consists of lifelong restriction of Phe intake by limiting the amount of natural protein in the diet, combined with administration of low Phe amino-acid mixtures and special low protein foods.
The success of treatment has, however, led to the discovery of secondary issues in the life-long outcome of PKU patients, including nutritional deficiencies in minerals, vitamins and long chain polyunsaturated fatty acids; as well as mineral bone disease.
In fact, prolonged natural protein dietary restriction may compromise calcium bonne absorption, leading to deficient mineralization and increased risk of fractures.
This study intends to evaluate the correlation between calcium ingestion through natural protein, synthetic amino acid mixtures intake and mineral bone density.

The development of this project may contribute to add knowledge regarding bone health status of PKU patients and enhance nutritional intervention in these patients, improving long-term patient´s outcome.

METHODOLOGY

The inclusion criteria will include all patients that have performed DEXA evaluation throughout follow-up, independently of age, gender or dietary compliance; with parental/ legal guardian consent.
Patients without DEXA evaluation or with missing data from their files that can compromise the data collection, will be excluded from the study.
Statistical analysis will be performed using IBM SPSS Statistics version 22. To evaluate the correlation between variables statistical tests will be used. All tests will be statistically significant when p value <,05.
Throughout the study we intend to address the following questions:
1. Do compliant patients have poor bone mineralization?
2. Is there a difference in the bone mineralization before and after puberty?
3. Do female patients have poor bone mineralization than male patients?
4. Did patient with poor bone mineralization developed fractures?
5. Was there a positive impact of dietary inclusion of dairy products in the patient´s bone mineralization?
6. Was there a positive impact of GMP supplementation in patient´s bone mineralization?
7. Was there a positive impact of Kuvan treatment in patient´s bone mineralization?
8. Did highly exercised patients have better bone mineral densities?

EXPECTED RESULTS

This is a retrospective study by clinical chart review of a cohort of PKU patients followed at the reference center for inborn errors of metabolism, CHULN.

After this study the investigation team expect to better understand the relation between PKU patient´s calcium intake and bone mineralization. Moreover, we expect to find out the impact of dietary compliance in bone health, especially in the occurrence of fractures. In addition, influence of gender, age, puberty status, exercise performance will also be addressed. Finally, we will analyze the calcium content of different amino acid mixtures, GMP and Kuvan treatment and correlate it with patient´s bone mineralization, which we expect to be helpful in the decision making concerning PKU patients follow up.