Date of Award

Winter 12-13-2023

Degree Type


Degree Name

Master of Science (MS)



First Advisor

Anita Marie Nucci

Second Advisor

Meriah Schoen


Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH).1 Phenylketonuria can have many forms, ranging from mild to severe (i.e., classic PKU) based on an individual’s Phenylalanine Hydroxylase (PAH) mutation.1 Phenylalanine Hydroxylase is a hepatic enzyme that converts the essential amino acid Phenylalanine (Phe) to tyrosine with the help of the cofactor tetrahydrobiopterin (BH4).1A deficiency in PAH or its cofactor BH4 results in Phe accumulation. An accumulation of Phe can be neurotoxic and lead to severe cognitive disabilities if left untreated.1 Newborn screening for inborn errors of metabolism is done 24-48 hours after birth.1If a newborn is confirmed of testing positive for PKU, they are brought to a metabolic clinic for confirmatory testing. The confirmatory testing tests the blood for plasma amino acids, or at a minimum plasma Phe and tyrosine (Tyr).2 The average cutoff for a positive screening based on is a PHE of 360 μmol/L and a PHE: TYR ratio >3.2 The mutation analysis is not required but recommended when screening newborn babies.

The primary treatment for PKU is through dietary restriction of Phe and supplementation with specifically designed medical foods (i.e., protein substitutes) to meet nutrient needs for growth and development.1,2The low Phe diet was established in 1953 by Bickel and colleagues.1 Phenylalanine is an essential amino acid that serves as a building block for high protein foods, such as red meats, milk, eggs, and yogurt.1,3 Most individuals with classical PKU have a dietary protein tolerance of less than 10 g/day (~500 mg Phe/day.3It is recommended that people with PKU maintain blood PHE between 120-360 μmol/L throughout their lifetime.3 The consequences of untreated PKU are brain dysfunction, mood alteration, nutritional deficiencies and severe brain damage.3 To prevent nutrient deficiencies in people with PKU, they consume fortified formulas and some do not track certain fruits and vegetables that are low protein to consume the nutrients that cannot consume in high protein foods.3 There are different types of diets that a person with PKU can follow depending on the severity of their PKU diagnosis. There is a low-protein diet and a simplified diet. The low-protein diet is the traditional treatment for PKU. The low-protein diet avoids all high protein foods and requires people with PKU to take an amino acid supplement to ensure nutrient requirements, growth, and health.4 The Simplified Diet Method is a specific a certain type of dietary management for the PKU population that allows unrestricted intake of foods low in Phe. These foods may include certain fruits, vegetables, and low-protein medical foods that would be considered, “free” or “unaccounted for”.5 The low Phe diet is a mainstay for treatment but there are challenges with it being too restrictive for people with PKU leading to poor quality of life and decreased adherence to diet. Current research has encouraged the development of simplified strategies in metabolic clinics to improve these aspects of life for the PKU population.2,3

There are different types of diets for people with PKU. The traditional diet is the most common where the individual with PKU must follow a Phe restricted diet according to their PKU diagnosis. The Simplified diet differs from the traditional diet in that the intake of Phe is reduced by approximately 30%, so they do not have to account for all Phe foods while tracking. So, there are different diets for individuals with PKU depending on their severity of diagnosis and how they prefer to manage their PKU.

There are very few educational materials on the use of the Simplified Diet as a dietary treatment for PKU infants 6-12 months. There is no data analyzing the relationship between the education of caregivers with PKU infants and the use of the Simplified Diet method. The creation of this educational handout for mothers with PKU infants 6-12 months will open more opportunity for new data to assess if diversifying a PKU infant earlier in their life would increase adherence to diet later in life, metabolic control, and increased nutrients consumption of fruits and vegetables that do not need to be counted in dietary Phe.

The specific aims of this project are: 1) to conduct a review of the literature to identify different strategies that increase dietary adherence, improve quality of life, and quality of the diet without reducing metabolic control. 2) to develop a simplified diet guide for caregivers with infants with PKU to try to increase adherence to diet later in life, metabolic control, and nutrient consumption of fruits and vegetables that do not need to be counted in dietary Phe.


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