Every year, an estimated 3-7 children in Norway are born with phenylketonuria (PKU), a rare genetic disorder characterized by an inability to break down phenylalanine. Researchers in Norway wanted to get a better understanding not only of PKU, but of the health impacts that eating protein (which contains phenylalanine) has on physical and neurological development. Discover the full study findings published in Nature Communications.

Phenylketonuria (PKU)

PAH gene mutations cause phenylketonuria (PKU), a rare genetic disorder. Normally, the amino acid phenylalanine is part of our diet; it can be found in meat, beans, cheese, and other forms of protein. An enzyme called phenylalanine hydroxylase (PAH) helps break down and remove phenylalanine from the body. However, PAH mutations cause patients to not have enough PAH. As a result, phenylalanine accumulates within the body, causing a variety of health problems. Because PKU is inherited in an autosomal recessive pattern, someone must inherit two defective genes in order to have this condition. An estimated 1 in every 10,000-15,000 births has PKU.

While symptoms do not typically appear directly after birth, many patients will show symptoms within a few months of life. These symptoms include:

• Intellectual and developmental delays
• Seizures
• Microcephaly
• Poor feeding
• Vomiting
• Hyperactivity
• Low bone strength
• Eczema and other skin rashes
• Musty-smelling skin, breath, or urine
• Fair skin and eyes
• Irritability
• Depression
• Tremors or abnormal muscle movements
• Heart defects

For patients with PKU, early diagnosis and treatment are crucial. Once a diagnosis is made, many patients are immediately transitioned to a PKU-friendly diet.

Mice Models

In this particular study, researchers created mice models of PKU using common PAH gene mutations, such as Pah-R261Q. They performed a variety of tests on both mice models of PKU, as well as “normal” or “wild-type” mice. Some of the findings included:

• Mice with PAH mutations typically had a higher weight and “altered lipid metabolism” than wild-type mice.
• When given the same food, wild-type mice used carbohydrates as a metabolic fuel source. Alternately, mice models of PKU used fat and protein. According to the researchers, this suggests that mice with PAH mutations had higher levels of oxidative stress. Medical News Today describes oxidative stress as:

  • an imbalance of free radicals and antioxidants in the body, which can lead to cell and tissue damage.

• Mice models of PKU had extremely high levels of mutated PAH aggregates in the liver, causing oxidative stress and difficulty in breaking these down.

Altogether, these findings suggest that PKU can have even more detrimental properties and cause more damage to the body than previously thought. This is not only due to the aggregates but to the result of oxidative stress. Researchers also suggest that these aggregates and oxidative stress could result in additional comorbidities. However, more research is needed to see if these findings are replicated in humans.

Read the source article on Medical XPress.