Brain imaging is unraveling the secrets of a rare disorder.
When a baby can’t metabolize an amino acid called phenylalanine into tyrosine, a precursor for dopamine and other important neurotransmitters, phenylalanine levels in the blood begin to rise. If not treated immediately serious brain-related health problems ensue, among them seizures, behavioral problems and intellectual disabilities.
Known as phenylketonuria, or PKU, the condition is an incurable genetic disorder. Once identified, afflicted infants must begin — and strictly adhere to for the rest of their lives — a phenylalanine-restricted diet. Because phenylalanine is found in many foods, especially those high in protein such as eggs, milk, nuts and meats, it is not an easy regimen to follow.
Because PKU is rare — the National PKU Alliance, a patient advocacy group, estimates that about 14,500 Americans are currently living with the condition — the disorder has received less attention from researchers than more common maladies. Investigations that have been completed focused mostly on exploring abnormalities in the white matter of PKU patients’ brains.
Shawn Christ, associate professor of psychological sciences and director of the MU’s Brain Imaging Center, and a group of his colleagues are seeking to expand that approach. “Only a handful of studies investigating the effects of PKU on gray matter have been conducted,” Christ says. “We decided to add to the body of knowledge on this understudied aspect in those affected by PKU.”
In their most recent study, published in the journal Molecular Genetics and Metabolism, Christ and his team spent nearly two years using advanced MRI imaging and detailed analytical techniques to map the gray matter of over 40 individuals both with and without PKU. The result produced evidence that there were significant gray-matter abnormalities even in individuals with PKU that has been treated early, and that these were most severe in the posterior regions of the brain.
In March, Christ and other delegates from the National PKU Alliance, which helped fund Christ’s study, met with the leaders from the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development to highlight the need for additional funding support for research on PKU and its health impact.
“We think that our research has the potential to contribute to better understanding the mechanisms underlying the abnormalities in brain and behavior associated with this disorder,” Christ says. “It may inform the development of new and exciting treatments for PKU.”