Diffusion kurtosis imaging detects subclinical white matter abnormalities in Phenylketonuria

Area of Science:

• Neurology
• Radiology
• Metabolic Disorders

Background:

• Phenylketonuria (PKU) is an inherited metabolic disorder causing neurological dysfunction due to phenylalanine buildup.
• Current PKU management focuses on phenylalanine levels, not direct measures of neurological damage.
• Conventional MRI lacks sensitivity to detect early, subclinical white matter changes in PKU.

Purpose of the Study:

• To investigate the utility of Diffusion Kurtosis Imaging (DKI) for detecting subclinical white matter abnormalities in adults with PKU.
• To identify and validate a sensitive DKI-based biomarker for assessing cognitive impairment and disease control in PKU.

Main Methods:

• A cohort study involving adults with PKU and healthy controls.
• Acquisition of MRI scans, neurocognitive assessments, and historical phenylalanine (Phe) levels.
• Development and testing of a candidate DKI metric (Krad/KFA ratio) derived from a case study and validated in a replication cohort.

Main Results:

• DKI revealed regionally-specific white matter abnormalities in PKU patients, even with normal conventional MRI.
• The Krad/KFA ratio effectively differentiated PKU patients from controls (p < 0.001).
• The Krad/KFA ratio correlated with attention deficits and medium-term phenylalanine control.

Conclusions:

• DKI can identify progressive, subclinical brain changes in PKU.
• The Krad/KFA ratio serves as a sensitive biomarker for cognitive impairment and PKU management.
• DKI offers a promising tool for monitoring end-organ damage in PKU.