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Global and regional volume changes in the brains of patients with phenylketonuria

From the Departments of Neurology (B.P.-D., J.C.) and Biochemistry (R.A., M.A.V.), Hospital Sant Joan de Déu, Universitat de Barcelona, and Institut d’Alta Tecnologia–PRBB, CRC Corporació Sanitària, Barcelona (J.P., C.S.-M., H.O.), Spain.

Address correspondence and reprint requests to Dr. Jaume Campistol, Neurology Department, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain; e-mail: campistol{at}hsjdbcn.org

Background: Although phenylketonuria is a treatable disease, patients with late or nonoptimal phenylalanine-restricted diet may experience brain damage. The authors used tridimensional MRI and a voxelwise analysis method to investigate possible volume changes in the brain parenchyma of patients with phenylketonuria.

Methods: The authors assessed 27 treated patients (mean age ± SD, 20 ± 7 years) and 27 matched control subjects. Global tissue volumes were compared, and statistical parametric maps of between-group regional volume differences were obtained for gray and white matter. Anatomic data were correlated with relevant clinical and biochemical variables.

Results: Patients with phenylketonuria showed smaller gray matter volumes that were associated with lower IQ and older age at diagnosis. Voxel-based maps revealed that significant gray matter volume reduction occurred in motor and premotor cortex and thalamus. A relative increase in gray matter volume was observed in the ventral part of the striatum. The authors found no group differences for global white matter measurements. Higher recent phenylalanine levels, however, were associated with larger global white matter volume in early-treated patients. Voxel-based maps showed a relative volume reduction in periventricular white matter and a relative increase in the region of the internal capsule, extending to the adjacent thalamus and striatum.

Conclusions: Treated patients may show significant gray and white matter volume changes related to the duration and strict observation of dietary treatment. Further studies are needed to investigate whether the presence of neurologic symptoms may be explained by specific anatomic alterations.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 11 issue to find the title link for this article.

Supported in part by the Spanish Grant FIS 021450. The first author has a grant from REDEMETH (G03/054).

Disclosure: The authors report no conflicts of interest.

Received July 28, 2005. Accepted in final form December 20, 2005.