1,721,011 research outputs found
Neurodevelopmental Disorder and Late‐Onset Degenerative Parkinsonism in a Patient with a WDR45 Defect
No full textBeta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant disorder due to a WDR45 defect that presents with the same phenotype in males and females [1].
WDR45 encodes for the WD40 repeat protein, which is involved in the biogenesis and maturation of autophagosomes due to its interaction with phosphoinositide 4 (WIPI4).
Clinical presentation of WDR45 defects is characterized by early-onset global developmental delay, epilepsy, and ataxia and evolves to severe intellectual disability and cognitive deterioration, dystonia, and parkinsonism after the second decade of life. Brain MRI diagnostic markers include iron deposition in the substantia nigra and globus pallidus and cerebral atrophy.
We report the clinical history of a female patient with a de novo WDR45 variant who presented with Angelman-like syndrome during childhood, years before the emergence of degenerative parkinsonism
Running apraxia as a presenting symptom of neuronal ceroid lipofuscinosis 6
No full text[No abstract available
Neurocognitive and neuroimaging outcome of early treated young adult PKU patients: A longitudinal study
No full textThe aim of the study was to explore the outcome of neurocognitive deficits and neuroimaging correlates in young adult early treated phenylketonuric (PKU) patients. We conducted a longitudinal study of 14 PKU patients that were assessed for IQ and neuropsychological functioning including executive functions (EF) over 14years of follow-up (age range at 1st and 2nd assessments were 7.8-13.5 and 22.2-27.7years, respectively). The IQ of all 14 PKU patients was within the normal range. With respect to the 1st assessment, mean IQ at follow-up did not decrease significantly. Compared to control subjects (n=14), mean IQ of patients was significantly lower (p=.0005). Throughout adolescence and early adulthood there was an improvement of neuropsychological functioning of PKU patients in spite of the relaxation of diet, however some deficits were still detectable when compared to controls. All patients that underwent a second MRI scan showed white matter alterations ranging from mild to severe which was correlated neither with IQ nor with EF scoring. Cognitive, neuropsychological and neuroimaging outcome was influenced from life-long and/or second decade of life metabolic control. Nevertheless patients' developmental trajectories were in some cases independent from metabolic control. Our results support the hypothesis of an individual vulnerability to phenylalanine. However, as long as individual factors that account for the vulnerability to Phe are not recognized, strict dietary control is recommended for all the patients also in the second decade of life
White matter involvement and neurocognitive outcome in phenylketonuric (PKU) patients with and without BH4/sapropterin dihydrochloride supplementation
No full textThe burden of epilepsy on long-term outcome of genetic developmental and epileptic encephalopathies: A single tertiary center longitudinal retrospective cohort study
Full text linkBackground: This retrospective cohort analysis highlighted neurodevelopmental outcome predictors of genetic developmental and epileptic encephalopathies (DEE). Patients and methods: Patients' demographic, clinical and molecular genetics data were collected. All patients underwent clinical, developmental, and neuropsychological assessments. Results: We recruited 100 participants (53 males, 47 females) with a mean follow-up lasting 10.46 ± 8.37 years. Age at epilepsy-onset was predictive of poor adaptive and cognitive functions (VABS-II score, r = 0.350, p = 0.001; BRIEF control subscale, r = -0.253; p = 0.031). Duration of epilepsy correlated negatively with IQ (r = -0.234, p = 0.019) and VABS-II score (r = -0.367, p = 0.001). Correlations were found between delayed/lacking EEG maturation/organization and IQ (r = 0.587, p = 0.001), VABS-II score (r = 0.658, p = 0.001), BRIEF-MI and BRIEF-GEC scores (r = -0.375, p = 0.001; r = -0.236, p = 0.033), ASEBA anxiety (r = -0.220, p = 0.047) and ADHD (r = -0.233, p = 0.035) scores. The number of antiseizure medications (ASMs) correlated with IQ (r = -0.414, p = 0.001), VABS-II (r = -0.496, p = 0.001), and BRIEF-MI (r = 0.294, p = 0.012) scores; while age at the beginning of therapy with ASEBA anxiety score (r = 0.272, p = 0.013). The occurrence of status epilepticus was associated with worse adaptive performances. The linear regression analysis model showed that delayed/lacking EEG maturation/organization had a significant influence on the IQ (R2 = 0.252, p < 0.001) and the BRIEF-GEC variability (R2 = 0.042, p = 0.036). The delayed/lacking EEG maturation/organization and the duration of epilepsy also had a significant influence on the VABS-II score (R2 = 0.455, p = 0.005). Conclusions: Age at seizure-onset, EEG maturation/organization, duration of epilepsy, occurrence of status epilepticus, age at the introduction and number of ASMs used are reliable predictors of long-term outcomes in patients with genetic DEE
Expert opinion of an Italian working group on the assessment of cognitive, psychological, and neurological outcomes in pediatric, adolescent, and adult patients with phenylketonuria
Full text linkPhenylketonuria (PKU) is an inherited metabolic disease characterized by a defective conversion of phenylalanine (Phe) to tyrosine, potentially leading to Phe accumulation in the brain. Dietary restriction since birth has led to normal cognitive development. However, PKU patients can still develop cognitive or behavioral abnormalities and subtle neurological deficits. Despite the increasing evidence in the field, the assessment of neurocognitive, psychopathological, and neurological follow-up of PKU patients at different ages is still debated. The high interindividual variability in the cognitive outcome of PKU patients makes the specificity of the neurocognitive and behavioral assessment extremely challenging. In the present paper, a multidisciplinary panel of Italian PKU experts discussed different tools available for cognitive, psychopathological, and neurological assessment at different ages based on the existing literature and daily clinical practice. This study aims to provide evidence and a real-life-based framework for a specific clinical assessment of pediatric, adolescent, and adult patients affected by PKU
Psychiatric disorders in adolescent and young adult patients with phenylketonuria
No full textBackground and objectives: Psychiatric symptoms are a challenging aspect in adolescent and adult early treated phenylketonuric (ETPKU) patients. To assess the occurrence of psychiatric disorders we explored the presence of symptoms requiring intervention and further investigated the link between psychiatric disorders, the quality of biochemical control and cognitive functioning.
Patients and methods: Forty-six ETPKU patients (aged 12 to 44) and 30 age-matched healthy controls were sub- jected to cognitive and psychiatric assessment by means of self-report questionnaires and psychiatric interview. Psychiatric diagnoses, if detected, were made according to DSM-5 criteria. Concomitant IQ, historical and concur- rent biochemical metabolic controls were included in the statistical analysis.
Results: Twenty-five out of 46 ETPKUs showed clinical scores on at least one scale of the psychiatric assessment (7/30 in controls); anxiety and withdrawal were the most frequent self-reported symptoms. Seventeen patients (and no controls) met criteria for a psychiatric diagnosis, most of them belonging to the Anxiety Disorders cate- gory. The occurrence of psychiatric symptoms was not associated with the life-long and concurrent quality of metabolic control but patients with good metabolic control (≤ 500 μM) in the first 11 years of life showed higher frequency of psychiatric diagnosis (Fisher's exact p = .0300).
Discussion/conclusion: ETPKUs show a higher than normal vulnerability to psychiatric disorders, which cannot be explained by the usual biochemical alterations influencing intellectual outcome. Our data support the hypothesis that the burden of the disease acts as psychological stress for children and their families. Possible involvement of neuromediators in the pathogenesis of these complex symptoms requires further investigation
Neuroimaging in early-treated phenylketonuria patients and clinical outcome: A systematic review
No full text: Lacking direct neuropathological data, neuroimaging exploration has become the most powerful tool to give insight into pathophysiological alterations of early-treated PKU (ETPKU) patients. We conducted a systematic review of neuroimaging studies in ETPKU patients to explore 1) the occurrence of consistent neuroimaging alterations; 2) the relationship between them and neurological and cognitive disorders; 3) the contribution of neuroimaging in the insight of neuropathological background of ETPKU subjects; 4) whether brain neuroimaging may provide additional information in the monitoring of the disease course. Thirty-eight studies met the inclusion criteria for the full-text review, including morphological T1/T2 sequences, diffusion brain imaging (DWI/DTI) studies, brain MRI volumetric, functional neuroimaging studies, neurotransmission and brain energetic imaging studies. Non-progressive brain white matter changes were the most frequent and precocious alterations. As confirmed in hundreds of young adults with ETPKU, they affect over 90% of ETPKU patients. Consistent correlations are emerging between microstructural alteration (as detected by DWI/DTI) and metabolic control, which have also been confirmed in a few interventional trials. Volumetric studies detected later and less consistent cortical and subcortical grey matter alterations, which seem to be influenced by the patient's age and metabolic control. The few functional neuroimaging studies so far showed preliminary but interesting data about cortical activation patterns, skill performance, and brain connectivity. Further research is mandatory in these more complex areas. Recurrent methodological limitations include restricted sample sizes concerning the clinical variability of the disease, large age-range, variable measures of metabolic control, and prevalence of cross-sectional rather than longitudinal interventional studies
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