White matter microstructural damage in early treated phenylketonuric patients.

BACKGROUND: Despite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)). METHODS: DTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Areas showing abnormal values in the patient group were correlated (Pearson) with age, lifetime Phe values, last year median and mean Phe, concurrent Phe values in plasma, urine neurotransmitters status biomarkers, and with a processing speed task. RESULTS: ETPKU showed bilaterally decreased MD values compared with HCs in the body and splenium of the corpus callosum, superior longitudinal fasciculus, corona radiata and in the posterior limb of the internal capsule. RD values followed a similar pattern, although decreased RD values in PKU patients were also found in the anterior limb of the internal capsule and in the cerebral peduncle. Decreased MD and RD values within the aforementioned regions had significant negative correlations with age, last year median and mean Phe and concurrent Phe values. No correlations were found with monoamines in urine or processing speed task. CONCLUSIONS: ETPKU patients showed MD and RD values significantly decreased across the whole brain when compared with HCs, and this damage was associated with high Phe values and the age of patients. Despite this microstructural damage, no affectation in processing speed was observed in patients with good metabolic control. DTI-MRI sequences could be used as a technique to quantify WM damage that is difficult to be detect in T1 or T2-weighted images, but also to quantify damage of WM through the follow up of patients with poor metabolic control in prospective studies.

Agenesis of the corpus callosum in a newborn with turner mosaicism.

The agenesis of the corpus callosum results from a failure in the development of the largest fiber bundle that connects cerebral hemispheres. Patient's outcome is influenced by etiology and associated central nervous system malformations. We describe a child with Turner syndrome (TS) mosaicism, with particular phenotype features and a complete agenesis of the corpus callosum. To our knowledge, this is the second case report of TS mosaicism associated with complete agenesis of the corpus callosum. Anatomical brain magnetic resonance imaging and diffusion tensor imaging were useful to confirm the complete absence of the corpus callosum, evaluate associated central nervous system malformations, visualize abnormal white matter tracts (Probst bundles) and assess the remaining commissures.