White matter microstructural damage in early treated phenylketonuric patients

Abstract

BackgroundDespite 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)).MethodsDTI-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.ResultsETPKU 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.ConclusionsETPKU 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.

Determining factors of the cognitive outcome in early treated PKU: A study of 39 pediatric patients

“…Despite early dietary treatment and adequate compliance, there is growing evidence of suboptimal neurocognitive outcomes in ETPKU patients, underlying the difficulties in predicting the outcomes in PKU. Brain imaging studies in ETPKU patients show white matter anomalies despite appropriate treatment compliance [8]. Recent studies reveal lower IQ scores compared to healthy controls, as well as attention and mood problems in children [9] and adult patients [10].…”

Effects of LC-PUFA Supplementation in Patients with Phenylketonuria: A Systematic Review of Controlled Trials

“…Evidence suggests that LC-PUFA supplementation may improve neurocognitive function, including motor skills [29], in PKU patients. Children with early-treated PKU can present structural alterations in cerebral white matter myelin [57,58,59] that may be associated with high Phe levels, but also with low DHA concentrations. However, because beneficial effects were reported in only one CT [29], and given the considerable variability across the studies included in this review in terms of the dose used, form of supplementation, functional outcome measures, and neurocognitive scales used, the available evidence is inconclusive.…”

La phénylcétonurie

“…Ces patients peuvent néanmoins récupérer, le plus souvent totalement, après une remise à un suivi strict du régime alimentaire. Des explorations neuroradiologiques en IRM (imagerie par résonnance magnétique) ont révélé des atteintes de la substance blanche, en particulier dans les zones périventriculaires postérieures [44,45]. Ces atteintes sont réversibles après un retour à un contrôle métabolique strict.…”