Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to apply the International Classification of Impairments, Disabilities and Handicap (ICIDH; WHO 1980) parallel to the Gross Motor Function Classification System (GMFCS; Palisano et al. 1997) in a population-based series of children with cerebral palsy (CP). Of the 116 children studied, birth characteristics, data on gross motor function, and level of handicap at 5 to 6 years of age, were retrospectively collected from medical records and documentation made by rehabilitation team members. Low handicap scores and mild levels of gross motor disability were present in children with hemiplegic CP, moderate scores in children with diplegic CP, simple ataxia, and athetotic CP, and high scores in children with dystonic CP and tetraplegic CP. A significant correlation was found between high handicap scores as well as high levels on the GMFCS and the presence of learning disability, epilepsy, and obvious aetiology of CP. A strong correlation was found between the handicap code and the GMFCS, the strongest concerning the dimension of mobility (r = 0.95,p<0.0001). A striking similarity in the grading of disability was present between the ICIDH handicap code and the GMFCS. The GMFCS is considerably less time-consuming and can be evaluated retrospectively. The handicap code requires more detailed information and is more useful for a comprehensive profile of the child.
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PMID:Correlation between ICIDH handicap code and Gross Motor Function Classification System in children with cerebral palsy. 1108 94

Rett syndrome, a neurodevelopmental disorder that is a leading cause of mental retardation in females, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). MECP2 mutations have subsequently been identified in patients with a variety of clinical syndromes ranging from mild learning disability in females to severe mental retardation, seizures, ataxia, and sometimes neonatal encephalopathy in males. In classic Rett syndrome, genotype-phenotype correlation studies suggest that X chromosome inactivation patterns have a more prominent effect on clinical severity than the type of mutation. When the full range of phenotypes associated with MECP2 mutations is considered, however, the mutation type strongly affects disease severity. MeCP2 is a transcriptional repressor that binds to methylated CpG dinucleotides throughout the genome, and mutations in Rett syndrome patients are thought to result in at least a partial loss of function. Abnormal gene expression may thus underlie the phenotype. Discovering which genes are misregulated in the absence of functional MeCP2 is crucial for understanding the pathogenesis of this disorder and related syndromes.
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PMID:Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations. 1126 31

Neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome and maternally inherited Leigh's syndrome have been associated with T8993G point mutations in the mitochondrial adenosine triphosphatase 6 gene. Typically, NARP syndrome is characterized by developmental delay, seizures, dementia, retinitis pigmentosa, ataxia, sensory neuropathy, and proximal weakness. Usually, there is a correlation between the percentage of mutated mitochondrial DNA and clinical severity, and when mutated mitochondrial DNA is > 90%, it is often seen with Leigh's syndrome. We now report a family with mitochondrial DNA T8993G mutation in eight living members, five with mutant mitochondrial DNA >90% and one with 20% mutant mitochondrial DNA. However, their clinical features include variable combinations of seizures, behavior problems, learning disability, mental retardation, sensorineural deafness, cerebellar ataxia, and proximal muscle weakness. No retinitis pigmentosa was found in all eight living members, including a 56-year-old grandmother. Only one dead female relative was diagnosed with Leigh's syndrome on the neuropathologic examination at age 22 years, when she died of an accident. High mitochondrial DNA T8993G mutation is not always associated with typical features of Leigh's and NARP syndromes.
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PMID:High mitochondrial DNA T8993G mutation (<90%) without typical features of Leigh's and NARP syndromes. 1145 54

Individuals with Angelman syndrome (AS) have severe learning disability,* ataxia, seizures, dysmorphic facies, a happy, sociable disposition, and inability to speak. Most of the literature concerning the clinical features of AS has concentrated on younger children. This study aimed to look at the natural history of AS by documenting the clinical features in a group of 28 adolescents and adults with AS (12 males, 16 females; age range 16 to 40 years). Specific aspects studied included physical characteristics, general health, mobility, seizure disorder, behaviour and communication, and self-help skills. Problems seen in this older group of individuals differed significantly from those typically observed in younger children. The incidence of scoliosis and joint contractures increased with age. Facial features were more striking in adults. Hyperactivity and concentration improved and the sociable disposition persisted. There were subtle clinical differences between the groups of individuals with different underlying genetic abnormalities. Information obtained from this study is relevant to diagnosis and management of older individuals with AS.
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PMID:Angelman syndrome: evolution of the phenotype in adolescents and adults. 1146 72

Knowledge on the effects of gabapentin (GBP) in learning disabled patients is limited. The objective of this study was to assess antiepileptic efficacy and tolerability of GBP in routine therapy. A retrospective open observational study design was applied. Twenty-nine consecutive residential patients with simple and/or complex partial seizures with or without secondary generalization and with different degrees of learning disability were included. All patients had severe therapy-resistant epilepsy. GBP was administered as add-on therapy. Dosages were progressively increased up to 1600-2400 mg/day (in a number of cases up to 4800 mg/day), in accordance with clinical requirements. The seizure frequency was recorded and compared between a baseline and a treatment period (after 3 months of titration) of 3 months duration each. Only three patients (10.3%) had a reduction of their seizure frequency by 50% or more. No patient became seizure-free. Unwanted side effects, mostly mild and dose-dependent, occurred in 37.9% of all patients. Somnolence and ataxia were the most frequently observed unwanted effects. In two cases hyperphagia/weight increase, and in two other cases edema occurred.We conclude the efficacy of GBP in learning disabled patients with highly therapy-resistant partial seizures is limited.
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PMID:Limited efficacy of gabapentin in severe therapy-resistant epilepsies of learning-disabled patients. 1463 May 2

Rapid brain growth occurs primarily during the third trimester in humans, whereas in rats it occurs after parturition. Therefore, we hypothesized that the effects of methylmercury (MeHg) on the postnatal developing rat nervous system may help in understanding the neurotoxicity on the human fetal brain when the brain is most vulnerable. In the present experiment, the dose-response effects of MeHg treatment during the postnatal developing phase in rats were studied. Male Wistar rats were orally administered 0, 1, 3, and 5 mg/kg/day methylmercury chloride (MMC), respectively, on postnatal day 1 and for 30 consecutive days. The body weight decline began from day 25 and typical symptoms, such as hind-limb crossing and ataxia, were observed in rats treated with 5 mg/kg/day MMC. The weight loss and typical symptoms were not observed in rats treated with 1 and 3 mg/kg/day. Mercury (Hg) concentrations in the brain were 2.6, 4.5, and 9.6 microg/g in the rats treated with 1, 3, and 5 mg/kg/day, respectively, on the day after the final MMC treatment. At 5 to 6 weeks of age, dose-dependent deficits of motor coordination in the rotarod test and learning disability in the passive avoidance response test were observed. Histopathological examination of a proportion of the MeHg-treated rats revealed widespread neuronal degeneration manifested by neuron loss and astrocytosis in the cerebral cortex, striatum, and cerebellum, where severity of the lesions seemed to increase in proportion to the administered dose of MMC. These findings using neonatal rats will be useful for better understanding of the effects of MeHg in the developing human brain during gestation.
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PMID:Dose-dependent effects of methylmercury administered during neonatal brain spurt in rats. 1535 5

It is currently thought that fragile X syndrome (FraX; the most common inherited form of learning disability) results from having more than 200 cytosine-guanine-guanine (CGG) trinucleotide repeats, with consequent methylation of the fragile X mental retardation (FMR1) gene and loss of FMR1 protein (FMRP). It was also considered that premutation carriers (with 55-200 CGG repeats) are unaffected, although a tremor/ataxia syndrome has recently been described in older adult male carriers. We reported that premutation expansion of CGG trinucleotide repeats affects brain anatomy, which, together with other studies, indicates that the molecular model for FraX needs modification. However, there are few studies on the cognitive ability of adult male premutation carriers. Thus, we selected 20 male premutation carriers on the basis of their genetic phenotype, and compared them to 20 male controls matched on age, IQ and handedness. We investigated intellectual functioning, executive function, memory, attention, visual and spatial perception, and language and pragmatics. The premutation carriers had significant impairments on tests of executive function (Verbal Fluency, Trail Making Test and Tower of London) and memory (Names sub-test of the Doors and People, Verbal Paired Associates Immediate Recall and Visual Paired Associates Delayed Recall sub-tests of the WMS-R, and Category Fluency Test for natural kinds). We therefore suggest that CGG trinucleotide repeats in the premutation range affect specific neuronal circuits that are concordant with specific neuropsychological deficits; and that these deficits reflect an emerging neuropsychological phenotype of premutation FraX.
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PMID:A neuropsychological investigation of male premutation carriers of fragile X syndrome. 1538 Oct 24

The suggested link between autism and cerebellar dysfunction formed the background for a Swedish clinical study in 2001. Thirty-two children (17 females, 15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of non-progressive congenital ataxia were examined, and parents were interviewed about the presence of neuropsychiatric problems in the child. Twelve children had simple ataxia, eight had ataxic diplegia, and 12 had 'borderline' ataxia. All but one of the 32 children had a mild to moderate gross motor disability according to Gross Motor Function Classification System (15 were categorized as level I, 16 as level II, and one child as level IV). Neuroimaging and neuropsychological testing were achieved in most cases. There was a strong association between learning disability* and autism spectrum disorder (often combined with hyperactivity disorder) on the one hand, and both simple and borderline 'ataxia' on the other, but a weaker link between ataxic diplegia and neuropsychiatric disorders. A correlation between cerebellar macropathology on neuroimaging and neuropsychiatric disorders was not supported. Congenital ataxia might not be a clear-cut syndrome of cerebellar disease, but one of many signs of prenatal events or syndromes, leading to a complex neurodevelopmental disorder including autism and learning disability.
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PMID:Ataxia, autism, and the cerebellum: a clinical study of 32 individuals with congenital ataxia. 1573 17

Congenital hypothyroidism (CH) is the commonest treatable cause of mental retardation. The prevelance is 1/3000 - 1/4000 live births worldwide. The importance of CH is that, the longer the diagnosis of CH is delayed, the higher the risk of mental retardation and neurologic sequale; such as poor motor coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning disability and diminished attention span. The most common cause of permenant CH is thyroid dysgenesis (85-90%) in which the transcription factors TTF1,TTF2 and PAX8 would appear to be obvious candidate genes in the aetiology. Especially cardiac defects and some other birth defects are described in patients with CH. Inborn errors of thyroid hormonogenesis are responsible for 10-15% of CH cases and usually have autosomal recessive inheritance, consistent with a single gene mutation. Transient CH is very common in prematures with an estimate of 10% of CH babies identified on newborn screening, or 1 in 40,000 neonates. CH neonates are usually symptom-free and the most encountered symptoms are prolonged jaundice, large fontanelles and umbilical hernia. In general, the extent of clinical findings depends on the cause, severity and duration of hypothyroidism. An elevated TSH>20 microm Iu/L and a decreased concentration of T4 confirms the diagnosis of CH. Infants with permanant abnormalities of thyroid function mostly have a serum TSH concentration > 50 microm Iu/L. Ultrasonography, thyroid scintigraphy, bone x ray of the knee and serum thyroglobulin concentration are the other essentials after diagnosis to clarify the status of the thyroid and the severity of hypothyroidism. The higher doses of 10- 15 microm g/kg/day and the commencement of treatment before 2 weeks gave rise to better long term outcome of CH patients. In the follow up of the patients noncompliance is the most important problem and serum freeT4 or T4 and TSH should be obtained at each visit to adjust the doses of L-thyroxine. Still a small number of patients with severe hypothyroidism in utero or reflected by clinical signs and symptoms extremely low T4 levels and delayed bone age may have intellectual deficits despite normal intelligence.
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PMID:Congenital hypothyroidism clinical aspects and late consequences. 1644 57

A de novo 4.1-megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array-based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 (SLC2A1 or GLUT1) gene. The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777). GLUT1 deficiency syndrome is characterized by therapy-resistant infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low concentration of glucose in the CSF. It is known that a ketogenic diet can lead to better control of seizures. This case study shows that identifying a microdeletion as the cause of learning disability is not only important for genetic counselling but might also lead to therapeutic intervention.
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PMID:A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development. 1748 14


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