Phenylketonuria (PKU) is an autosomal recessive disorder where the patient has an elevated level of phenylalanine, a type of amino acid, in their blood. Unlike healthy individuals, phenylketonuria patients cannot metabolise phenylalanine, the concentration of the amino acid builds up over time in the bloodstream. A patient must have received two copies of the mutated gene – one copy from each parent – to have the disorder. Where an individual receives only one copy of the mutated gene, they are a carrier and do not exhibit any symptoms but may pass on their defective gene to their offspring.
Over time, the accumulation of phenylalanine stunts the brain’s development. In the past, when little was known about the disorder and there were no measures in place to allow for early diagnosis, most individuals with phenylketonuria suffered from profound intellectual disabilities. Today, most cases of phenylketonuria are diagnosed early during newborn screening procedures to allow intervention as soon as possible. Intervention comes in the form of adhering to diets containing low levels of phenylketonuria, and if this is commenced early enough, is effective in preventing most complications associated with the disorder. However, the diet can be restrictive and has a low level of compliance with older patients, resulting in brain damage over time.
Cognitive issues associated with phenylketonuria
Severe cases of phenylketonuria, if not treated in time, can cause permanent brain damage. This is also referred to classic phenylketonuria. Symptoms include seizures, behavioural problems, and severe psychological disorders. Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactive Disorder (ADHD) also have higher prevalence rates among individuals with phenylketonuria.
In general, the severity of the complications highly correlates with levels of blood phenylalanine. However, even in mild cases where blood phenylalanine concentrations are low, patients still have relatively poor executive function compared to healthy controls. Working memory and attentional shifting are most profoundly affected, as is overall cognitive function and processing speed.
Individuals with phenylketonuria also face impairments in social cognition over their lifetime. As children, they may exhibit behavioural problems and as adults, they are more prone to emotional issues including social isolation and low self-esteem. In some cases, they may also find social situations and communicating with others to be challenging.
Treatment for phenylketonuria
This will depend on the level of severity and the types of processing, emotional and behavioural issues present. Treatment needs to be individualised according to a thorough neuropsychological assessment.