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Psychomotor Retardation (psychomotor + retardation)
Kinds of Psychomotor Retardation Selected AbstractsNovel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations,HUMAN MUTATION, Issue 1 2009W. Edward Visser Abstract Monocarboxylate transporter 8 (MCT8; approved symbol SLC16A2) facilitates cellular uptake and efflux of 3,3,,5-triiodothyronine (T3). Mutations in MCT8 are associated with severe psychomotor retardation, high serum T3 and low 3,3,,5,-triiodothyronine (rT3) levels. Here we report three novel MCT8 mutations. Two subjects with the F501del mutation have mild psychomotor retardation with slightly elevated T3 and normal rT3 levels. T3 uptake was mildly affected in F501del fibroblasts and strongly decreased in fibroblasts from other MCT8 patients, while T3 efflux was always strongly reduced. Moreover, type 3 deiodinase activity was highly elevated in F501del fibroblasts, whereas it was reduced in fibroblasts from other MCT8 patients, probably reflecting parallel variation in cellular T3 content. Additionally, T3-responsive genes were markedly upregulated by T3 treatment in F501del fibroblasts but not in fibroblasts with other MCT8 mutations. In conclusion, mutations in MCT8 result in a decreased T3 uptake in skin fibroblasts. The much milder clinical phenotype of patients with the F501del mutation may be correlated with the relatively small decrease in T3 uptake combined with an even greater decrease in T3 efflux. If fibroblasts are representative of central neurons, abnormal brain development associated with MCT8 mutations may be the consequence of either decreased or increased intracellular T3 concentrations. Hum Mutat 0,1-10, 2008. © 2008 Wiley-Liss, Inc. [source] Apathy and cognitive performance in older adults with depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2003Denise Feil Abstract Objectives Recent studies have linked apathy to frontal lobe dysfunction in persons with dementia, but few studies have explored this relationship in older, depressed persons without dementia. We examined the association between apathy and cognitive function in a group of older persons with major depression using standardized neuropsychological tests. We hypothesized that presence of apathy in depression is associated with poorer frontal executive performance. Methods We analyzed data from 89 older adults with major depression. We defined apathy using four items from the Hamilton Psychiatric Rating Scale for Depression which reflect the clinical state of apathy, including ,diminished work/interest,' ,psychomotor retardation,' ,anergy' and ,lack of insight.' Results Apathy most strongly correlated with two verbal executive measures (Stroop C and FAS), a nonverbal executive measure (Wisconsin Card Sorting Test,Other Responses), and a measure of information processing speed (Stroop B). Apathy was not associated with age, sex, education, medical illness burden, Mini-Mental State Examination score and Full Scale IQ score. Stepwise regression analyses of significant cognitive tests showed that apathy alone or apathy plus depression severity, age, or education accounted for a significant amount of the variance. Conclusions The results of this study provide support for an apathy syndrome associated with poorer executive function in older adults with major depression. Copyright © 2003 John Wiley & Sons, Ltd. [source] Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD geneJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2001Sankar Surendran Abstract Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a ,5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency. J. Neurosci. Res. 65:591,594, 2001. © 2001 Wiley-Liss, Inc. [source] L-2-Hydroxyglutaric Aciduria in Staffordshire Bull TerriersJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2003Carley J. Abramson L-2-Hydroxyglutaric aciduria is an inborn error of metabolism, which has been recognized in humans since 1980. The metabolic defect responsible for the disease is unknown, but the disorder can be diagnosed in humans by elevations of the organic acid, L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF), plasma, and urine of affected patients. The disorder produces a variety of clinical neurological defects in humans including psychomotor retardation, seizures, and ataxia. There have previously been no recognized animal models of the disease. However, 6 Staffordshire Bull Terriers were recently identified with the disorder. The animals presented with a variety of clinical signs, most notably seizures, ataxia, dementia, and tremors. They were all screened for organic acid abnormalities in urine, and CSF and plasma (when available). Levels of L-2-hydroxyglutaric acid were elevated in all body fluids evaluated. The clinical, clinicopathologic, and magnetic resonance imaging (MRI) characteristics associated with L-2-hydroxyglutaric acid in Stafforshire Bull Terriers is reported herein and represents the first veterinary model of this inborn error of metabolism. [source] Oculocutaneous albinism associated with multiple malformations and psychomotor retardationPEDIATRIC DERMATOLOGY, Issue 2 2010MAGDALENA BUDISTEANU M.D., PH.D. To our knowledge, this association has not been previously described. [source] New mental retardation syndrome associated with ocular colobomas, cleft palate, and genital, skeletal, and craniofacial abnormalitiesAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2002M.M. Khalifa Abstract We describe three Canadian brothers of Cree origin, with a previously undescribed pattern of malformation including distinctive craniofacial abnormalities with triangular facies, hypertelorism, low-set and posteriorly rotated ears, ocular colobomas, ptosis, brachycephaly with widely separated sutures, cleft soft palate, undescended testes, bifid scrotum and hypospadius, wide webbed neck, webbed fingers, pectus excavatum and hypersegmented sternum, and severe psychomotor retardation. The presence of normal brain imaging and physical growth distinguishes them from other syndromes with overlapping abnormalities. This is either an X-linked or autosomal recessive condition. © 2001 Wiley-Liss, Inc. [source] Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiencyANNALS OF NEUROLOGY, Issue 1 2010Cigdem I. Akman MD Objective Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired microcephaly, infantile-onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5-hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain. Methods Thirteen Glut1-DS patients completed a 5-hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well-being. All patients had a full neuropsychological battery prior to OGTT. Results The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well-being were observed without any change in memory performance. Interpretation This study documents transient neurological improvement in Glut1-DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood-brain barrier. The transient improvement in brain function underscores the rate-limiting role of glucose transport and the critical minute-to-minute dependence of cerebral function on fuel availability for energy metabolism. ANN NEUROL 2010;67:31,40 [source] Inhibition of defective adenylosuccinate lyase by HNE: A neurological disease that may be affected by oxidative stressBIOFACTORS, Issue 1-4 2005C. Crifò Abstract Adenylosuccinate lyase is an enzyme of fumarase superfamily that participates in the purine biosynthetic pathway, catalysing the nonhydrolytic cleavage of succinyl groups from SAICA ribotide and adenylosuccinate. Enzyme defects are associated with a human inherited disease, which arises from single point mutations to the gene and results in mild to severe psychomotor retardation, epilepsy, muscle wasting, and autistic features. Adenylosuccinate lyase activity is lost to a different extent in the patients. Diminished levels of enzyme have been attributed to loss of catalytic activity, protein instability, or environmental factors. P100A/D422Y mutation represents a feasible model for studying the effect of cell milieu on the activity of the impaired enzyme. The defective enzyme is inhibited by micromolar concentrations of trans-4-hydroxy-2-nonenal (HNE), a major product of membrane peroxidation that has been found to accumulate in brain tissues of patients with neurodegenerative disorders. It is suggested that inactivation of defective adenylosuccinate lyase by HNE and other membrane peroxidation products may account, at least in part, for the impairment of neurological functions and recurrent worsening of the symptoms. [source] Bipolar depression: phenomenological overview and clinical characteristicsBIPOLAR DISORDERS, Issue 6 2004Philip B Mitchell Objectives:, There has been increasing interest in the depressed phase of bipolar disorder (bipolar depression). This paper aims to review the clinical characteristics of bipolar depression, focusing upon its prevalence and phenomenology, related neuropsychological dysfunction, suicidal behaviour, disability and treatment responsiveness. Methods:, Studies on the prevalence of depression in bipolar disorder, the comparative phenomenology of bipolar and unipolar depression, as well as neuropsychology and brain imaging studies, are reviewed. To identify relevant papers, a literature search using MEDLINE and PubMed was undertaken. Results:, Depression is the predominant mood disturbance in bipolar disorder, and most frequently presents as subsyndromal, minor or dysthymic depression. Compared with major depressive disorder (unipolar depression), bipolar depression is more likely to manifest with psychosis, melancholic symptoms, psychomotor retardation (in bipolar I disorder) and ,atypical' symptoms. The few neuropsychological studies undertaken indicate greater impairment in bipolar depression. Suicide rates are high in bipolar disorder, with suicidal ideation, suicide attempts and completed suicides all occurring predominantly in the depressed phase of this condition. Furthermore, the depressed phase (even subsyndromal) appears to be the major contributant to the disability related to this condition. Conclusions:, The significance of the depressed phase of bipolar disorder has been markedly underestimated. Bipolar depression accounts for most of the morbidity and mortality due to this illness. Current treatments have significant limitations. [source] Defining the best available treatment for neurocytomas in childrenCANCER, Issue 11 2004Dirk Rades M.D. Abstract BACKGROUND In children, neurocytomas are extremely rare tumors in the central nervous system. Since this entity was introduced in 1982, approximately 60 cases have been reported among patients age , =18 years of age. The current analysis was performed to define the best available neurocytoma therapy in children. METHODS All reported neurocytoma cases were reviewed for age, extent of resection, radiotherapy, radiotherapy dose, local control, and survival. Data were obtained from the literature and the authors. Statistical analysis was performed with the Kaplan,Meier method and log-rank test. RESULTS Fifty-nine children were categorized by therapy: complete tumor resection (CTR; n = 20), complete tumor resection plus radiotherapy (CTR-RT; n = 11), incomplete tumor resection (ITR; n = 14), and incomplete tumor resection plus radiotherapy (ITR-RT; n = 14). Local control rates were better after CTR, CTR-RT, and ITR-RT than after ITR, at 5 years (86%, 100%, and 100% vs. 60%; P < 0.001) and at 10 years (86%, 100%, and 100% vs. 45%; P < 0.001). The 5-year and 10-year survival rates were 100% after CTR, 100% after CTR-RT, 100% after ITR-RT, and 93% after ITR (P = 0.4). In the ITR-RT group, no difference was observed between doses , 50 gray (Gy) and , 54 Gy when compared for local control (P = 1.0) and survival rates (P = 1.0). Radiotherapy-related psychomotor retardation or secondary brain tumors were not reported. CONCLUSIONS The prognosis of children with neurocytomas is extremely good. CTR was associated with better local control and survival rates than ITR. After ITR, radiotherapy improves local control, but not survival. If postoperative radiotherapy is considered, a dose of 50 Gy was appropriate for long-term local control in children, whereas higher doses were required in adults. Cancer 2004. © 2004 American Cancer Society. [source] Decreased bone density and treatment in patients with autosomal recessive cutis laxaACTA PAEDIATRICA, Issue 3 2009C Noordam Abstract Aim: Due to the occasional association pathological fractures and osteoporosis we evaluated four patients with cutis laxa syndrome for skeletal anomalies. Patient/Methods: We prospectively evaluated four patients, a male and a female child and a brother-sister sib pair, with dysmorphic features, growth delay, joint anomalies, psychomotor retardation and congenital cutis laxa. The clinical features and the family history were suggestive for autosomal recessive cutis laxa syndrome type II, partially overlapping with geroderma ostedysplastica. Skeletal survey, sequential bone density measurements, endocrine and metabolic investigations were performed including N- and O-linked glycosylation analysis. ATP6V0A2 and FBLN5 mutations were ruled out in all patients. Results: All children were diagnosed with significantly decreased bone density, especially in the lumbar spine, including spontaneous vertebral and rib fractures in three children. Following 24 months of bisphosphonate treatment a total restitution of bone density was observed in three cases and no relapse was detected in the 2-year follow-up period. A spontaneous improvement was found in one female during puberty. Conclusion: Bone disease might occur early in the course in autosomal recessive cutis laxa syndrome. We report on a significant clinical improvement and stabilization in our patients following bisphosphonate therapy. We suggest early, systemic evaluation and follow up of bone density in all children presenting with inherited cutis laxa. [source] Minor neurological dysfunction, cognitive development and somatic development at the age of 3 to 11 years in very-low-birthweight infants with transient periventricular echodensitiesACTA PAEDIATRICA, Issue 12 2006JOERG KUTSCHERA Abstract Aim: To determine, using strict exclusion criteria, whether transient periventricular echodensities (TPE) in very-low-birthweight infants lead to minor neurological dysfunction and problems in cognitive and somatic development in children without major neurological impairments. Methods: 23 children with TPE were matched to 23 children without TPE. Exclusion criteria were small for gestational age, microcephaly at birth, diplegia, asphyxia, psychomotor retardation, intraventricular haemorrhage grade III/IV, major surgical interventions and malformations. The Kaufman Assessment Battery for Children, Draw-a-Man Test and neuropaediatric examination were used for evaluation. Results: There were no differences in demographic data, growth and socio-economic status. Significant differences with lower results in the TPE group were found in fine motor skills and in the Draw-a-Man Test. In the Kaufman Assessment Battery for Children, all subscales were below average in the TPE group, except the sequential processing scale. In the control group, all subscales were within the average range. Conclusion: By using strict exclusion criteria to eliminate other risk factors for minimal neurological dysfunction and poor cognitive development, we were able to focus on the effect of TPE. TPE seem to affect cognitive development and cause minor neurological dysfunction. [source] West syndrome and mitochondrial diabetes: relationship or coincidence?CLINICAL ENDOCRINOLOGY, Issue 1 2002B. Bouhanick Summary West syndrome occurs in infancy and in early childhood. It is characterized by intractable seizures occurring almost daily, severe psychomotor retardation, poor prognosis and EEG abnormalities, known as hypsarrhythmia. We report here the case of a 28-year-old patient, who was diagnosed with West syndrome when he was 8 months old and with diabetes mellitus when he was 25 years old. Sequencing analyses and restriction analyses were suggestive of mitochondrial diabetes. Four years after the diagnosis of diabetes, this patient's diabetes is still controlled by diet and biguanides. [source] Free sialic acid storage (Salla) disease in SwedenACTA PAEDIATRICA, Issue 12 2002A Erikson The first 23 patients diagnosed with Salla disease in Sweden are presented. A high incidence of the "Finnish" R39C mutation, together with genealogical data, indicates that a large proportion of the mutations are of Finnish origin. All patients had pathologically high levels of free sialic acid in urine and in fibroblasts. The clinical picture confirms what has already been reported from Finland, with early psychomotor retardation, ataxia and speech problems. One-third of the patients had epilepsy. Conclusions: Salla disease is more common in Sweden than supposed. A large proportion of the mutated alleles seem to be of Finnish origin. The clinical picture is the same as that reported from Finland. [source] | |||||||||||||