Study on MRI changes in phenylketonuria in patients referred to mofid hospital/iran (original) (raw)

Biochemical, clinical and neuroradiological (MRI) correlations in late-detected PKU patients

Journal of Inherited Metabolic Disease, 1995

Brain magnetic resonance imaging (MRI) was performed in 17 latedetected PKU patients (aged 2.8-25 years). Twelve subjects had been treated late (0.7-4.5 years), and 5 not at all. Four were still on diet when the study was performed. Mental development was normal in 4 subjects, mildly retarded in 6, and moderately or severely retarded in 7. None had exhibited mental or neurological deterioration. On MRI examination a symmetrical increase of T2-weighted signal in the periventricular white matter was found in all patients, although to different degrees. Concomitant signal decrease on the Tl-weighted sequences was detected in 9 patients. Ten subjects showed focal white-matter abnormalities. A variable degree of cortical and subcortical atrophy was found in 12 subjects, and asymmetry of lateral ventricles in 4.

Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels

Journal of neurodevelopmental disorders, 2024

Background Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce. Objectives This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU. Methods Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner. FreeSurfer (v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p < 0.05). Results Adult patients with PKU showed significantly lower performance than HC in Full Scale IQ (t = 2.67; p = .010) from the WAIS-IV. The PKU group also showed significantly lower volumes than HC in the pallidum (U = 224.000; p = .008), hippocampus (U = 243.000; p = .020), amygdala (U = 200.000; p = .002), and brainstem (t = 3.17; p = .006) as well as in total cerebral white matter volume (U = 175.000; p = .001). Blood phenylalanine (Phe) levels in PKU patients were negatively correlated with the pallidum (r =-0.417; p = .013) and brainstem (r =-0.455, p = .006) volumes. Conclusions Adult patients with early-treated PKU showed significantly lower global intelligence than HC. Moreover, these patients showed reduced global white matter volume as well as reductions in the volume of several subcortical grey matter structures, which might be related to the existence of underlying neurodevelopmental alterations. Higher blood Phe levels were also negatively correlated with pallidum and brainstem, suggesting a higher vulnerability of these structures to Phe toxicity.

MR imaging and spectroscopy in PKU

Mental Retardation and Developmental Disabilities Research Reviews, 1999

Phenylketonuria (PKU) is an autosomal recessive disorder that results in the accumulation of phenylalanine in the blood and soft tissues. Elevated levels of phenylalanine have neurotoxic effects on the developing brain, resulting in mental retardation. Early diagnosis and treatment limits the neurological damage. Magnetic resonance imaging (MRI) changes are seen in the white matter on T 2 weighted imaging in many subjects. The severity of the changes do not correlate with clinical measures of neurological health. The changes correlate best with recent phenylalanine control. The levels of brain phenylalanine concentration using magnetic resonance spectroscopy (MRS) have been shown not to correlate tightly with the blood phenylalanine concentration. The individual variation in the brain to blood phenylalanine is large. This individual variability may be responsible for different clinical outcomes in PKU subjects who have similar long-term blood concentrations of phenylalanine.

Neuroradiological findings of an adolescent with early treated phenylketonuria: is phenylalanine restriction enough?

Clinics and practice, 2011

Phenylketonuria is caused by mutations in the enzyme phenylalanine hydroxylase gene, that can result in abnormal concentrations of phenylalanine on blood, resulting in metabolites that can cause brain damage. The treatment is based on dietary restriction of phenylalanine, and noncompliance with treatment may result in damage of the brain function. Brain abnormalities can be seen on magnetic resonance imaging of these individuals. Studies indicate that the appearance of abnormalities in white matter reflects high levels of phenylalanine on the blood. This case will show the clinical and neuroradiological aspects of a teenager with constant control of phenylalanine levels. Despite the continuous monitoring and early treatment, the magnetic resonance imaging identified impressive abnormalities in the white matter. This leads us to one question: is the restriction of phenylalanine sufficient to prevent changes in the white matter in patients with phenylketonuria?

Prolonged exposure to high and variable phenylalanine levels over the lifetime predicts brain white matter integrity in children with phenylketonuria

Molecular Genetics and Metabolism, 2015

In this study, we retrospectively examined the microstructural white matter integrity of children with early-and continuously-treated PKU (N = 36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure,

Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria

Neuroradiology, 2009

Introduction The aim of this study was to grade magnetic resonance white matter abnormalities (WMAs) of classical phenylketonuria (cPKU) patients treated from birth and to compare sensitivity and specificity of T2-weighted and diffusion-weighted images (DWI). Methods Twenty early-treated cPKU patients still on a lowphenylalanine diet (12 males; mean age 21.2 years) and 26 normal subjects (ten males; mean age 25.1 years) were enrolled. Typical T2-and diffusion-weighted WMAs were semiquantitatively graded according to Thompson score (TS). Besides, a regional magnetic resonance imaging (MRI) score (mTS) was developed according to extension and intensity of WMAs. Phenylalanine and tyrosine plasma

Unusual Case of Phenylketonuria With Atypical Brain Magnetic Resonance Imaging Findings

Journal of Child Neurology, 2012

Phenylketonuria is a treatable inborn error of amino acid metabolism caused by deficiency of the enzyme phenylalanine hydroxylase, responsible for converting phenylalanine to tyrosine. We report a 10-month-old boy with psychomotor regression and infantile spasms. He was diagnosed with classic phenylketonuria and West syndrome. Treatment was initiated with phenylalanine-restricted diet and vigabatrin. After 5 months of treatment, he persists with developmental delay, severe hypotonia, swallowing disorder, and drug-resistant epilepsy. Brain magnetic resonance imaging showed the typical abnormalities in supratentorial white matter and exceptional infratentorial and basal ganglia compromise. Severity of white matter abnormalities and neurologic symptoms correlates with blood levels of phenylalanine. Infratentorial changes occur in severe cases. Other mechanisms could take part in cases like this with atypical neuroimaging abnormalities of the basal ganglia.

MR in phenylketonuria-related brain lesions

Acta Radiologica, 2001

Key words: Brain, phenylketonuria; techniques to explain the pathological changes observed in periventricular white MR imaging, diffusion; spectroscopy. brain matter using conventional MR imaging.