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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Careful clinical delineation and advances in analytical methods have opened new possibilities for the detection of inherited neurometabolic disorders, some of which require specific CSF analyses for diagnosis. Although patients suffering from these disorders have recognizable phenotypes, there are strong indications that remain many undiagnosed, leading to a continuation of futile diagnostic searches and, for most disorders, withholding of available rational therapy. As there is still widespread uncertainty about when to perform specialist CSF investigations, it is the aim of this paper to define the place for CSF investigations in the diagnostic work-up of a child with an encephalopathy of unknown origin. Most neurometabolic disorders can be identified through serum, plasma and urine analyses in conjunction with neuroradiological investigations. Whenever CSF investigations are performed, the analysis should include quantitative determination of lactate, pyruvate and amino acids, the latter by methods especially suited for CSF, in addition to cells, glucose, protein, immunoglobulin classes, specific immunoglobulins, and an evaluation of the blood-brain barrier. If the disease course is non-progressive or if extracerebral symptoms are present in addition to an encephalopathy, e.g. endocrinological, hepatic, muscular or renal symptoms, investigations of metabolites in CSF over and above lactate, pyruvate and amino acids are generally noncontributary. Specific CSF investigations, which are discussed in detail, test metabolic pathways of brain metabolism, especially of neurotransmission. For a successful diagnosis of these defects, analyses must be planned individually, before CSF samples are taken, based on family history, clinical findings and disease course. Different determinations require different logistics from taking of the sample to shipment. One indication for specialized CSF analyses including biogenic monoamines and GABA is severe neonatal/infantile epileptic encephalopathy. In addition to a therapeutic trial of B6, folinic acid should be tried empirically for two to three days as the emerging syndrome of folinic acid responsive seizures appears to be the underlying cause in a sizable proportion of patients. In later infancy and childhood, defects in the metabolism of the biogenic monoamines may be suspected in patients with (fluctuating) extrapyramidal disorders, in particular Parkinsonism dystonia or more general "athetoid cerebral palsy", and vegetative disturbances. A severe epileptic encephalopathy and progressive mental retardation may be present. Neuroimaging findings do not show specific lesions. Determinations of folates and organic acids in CSF appear at present only warrantable individually in special constellations, e.g. classical clinical findings and disease course suggestive of glutaryl-CoA dehydrogenase deficiency with repeated negative quantitative analyses of organic acids in urine. The diagnosis of disorders, which require specific analyses of CSF, can only be achieved by conscious diagnostic decisions based on a concept of the respective disease and repeated scrupolous expert clinical evaluation aided by an array of investigations in blood and urine as well as neuroimaging findings. No single one investigation in CSF can serve as a "selective screening" test. A growing awareness of these disorders is needed and should lead to increased and earlier diagnosis of patients through fewer rather than more lumbar punctures.
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PMID:Cerebrospinal fluid investigations for neurometabolic disorders. 963 60

We observed a young patient with slight mental retardation, suffering from drug-resistant tonic-clonic seizures, who presented a status epilepticus (SE), in two separate periods when valproic acid (VPA) was added to the phenobarbital (PB) already being used in the patient's therapy. The VPA-induced SE was characterized by normal plasma levels of antiepileptic drugs (AEDs), normal ammonemia and normal liver function. The case we studied represents the first report on a VPA-induced SE. Furthermore the case confirms that VPA, as well as causing encephalopathy secondary to hyperammonemia, may also provoke a primary involvement of the central nervous system (CNS), specially when used in young epileptic, mentally retarded subjects. In an attempt to explain the paradoxical effect of VPA we hypothesise that the SE could be due to an increase in excitatory activity producing a consequent epileptogenic effect in those subjects with a predisposition for toxic reaction to VPA therapy due to congenital anomalies of neural networks.
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PMID:Valproate-induced epileptic tonic status. 970 Aug 38

Magnetic resonance imaging (MRI) has enabled the identification of neuronal migration disorders in living subjects. This represents an important achievement in the diagnosis of patients with these anomalies. At least five affected families with coexistent subcortical laminar heterotopia and lissencephaly have been reported recently. This association suggests an X-linked pattern of inheritance. In the family that we report, the mother suffered from epilepsy and the oldest daughter from epilepsy and mental retardation. Both patients showed subcortical laminar heterotopia on MRI. The youngest son presented a severe encephalopathy with early onset seizures, and was found to show lissencephaly on MRI. The other two siblings, a boy and a girl, had no neurological abnormalities. The severity of these patients' clinical symptoms were clearly related to MRI findings.
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PMID:X-linked subcortical laminar heterotopia and lissencephaly: a new family. 981 May 65

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.
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PMID:D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? 989 84

The Consensus Conference of the American College of Medical Genetics has established guidelines regarding the evaluation of patients with mental retardation (MR) [Curry et al., Am. J. Med. Genet. 72:468-477, 1997]. They emphasized the high diagnostic utility of cytogenetic studies and of neuroimaging in certain clinical settings. However, data on the diagnostic yield of these studies in well-characterized populations of individuals with MR are scant. Majnemer and Shevell [J. Pediatr. 127:193-199, 1995] attained a diagnostic yield of 63%. However, this study included only 60 patients and the classification included pathogenetic and causal groups. The Stella Maris Institute has evaluated systematically patients with developmental delay (DD)/MR and performed various laboratory studies and neuroimaging in almost all patients. We report a retrospective analysis of the diagnostic yield of 120 consecutive patients observed at our Institute during the first 6 months of 1996. There were 77 males and 43 females; 47 were mildly delayed (IQ 70-50), 31 were moderately delayed (IQ 50-35), and 42 were severely delayed (IQ 35-20). Diagnostic studies (history, physical examination, standard cytogenetics, fragile X testing, molecular studies, electroencephalography, electromyography, nerve conduction studies, neuroimaging, and metabolic screening tests) yielded a causal diagnosis in 50 (41.6%) and a pathogenetic diagnosis in 47 (39.2%) of the 120 patients. Causal categories included chromosomal abnormalities (14), Fra(X) syndromes (4), known MCA/MR syndromes (19), fetal environmental syndromes (1), neurometabolic (3) disorders, neurocutaneous (3) disorders, hypoxic-ischemic encephalopathy (3), other encephalopathies (1), and congenital bilateral perisylvian syndrome (2). Pathogenetic categories included idiopathic MCA/MR syndromes (35), epileptic syndromes (10), and isolated lissencephaly sequence (2). Diagnostic yield did not differ across categories and degree of DD. Our results, while confirming the diagnostic utility of cytogenetic/molecular genetic, and neuroimaging studies, suggest the usefulness of accurate electroencephalogram recordings, and stress the importance of a thorough physical examination. Referral to a university child neurology and psychiatry service, where a comprehensive assessment with a selected battery of investigations is possible, yields etiologic findings in a high percentage of DD/MR patients, with important implications for management, prognosis and recurrence risk estimate.
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PMID:Diagnostic yield of the comprehensive assessment of developmental delay/mental retardation in an institute of child neuropsychiatry. 991 45

Two brothers are described who had juvenile-onset DHPR deficiency. Both were considered normal until six years of age when they developed a fluctuating and progressive encephalopathy combining mental retardation, epilepsy, pyramidal, cerebellar and extrapyramidal signs.
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PMID:Juvenile form of dihydropteridine reductase deficiency in 2 Tunisian patients. 1002 53

We describe 2 new cases of Alexander's disease, the first to be reported in Belgium. The first patient, a 4-year-old girl, presented with progressive megalencephaly, mental retardation, spastic tetraparesis, ataxia and epilepsy: post-mortem examination showed widespread myelin loss with Rosenthal fibers (RFs) accumulation throughout the neuraxis. She was the third of heterozygotic twins, the 2 others having developed normally and being alive at age 5 years. The second patient developed at age 10 years and over a decade spastic paraparesis, palatal myoclonus, nystagmus, thoracic hyperkyphosis and thoraco-lumbar scoliosis with radiological findings of bilateral anterior leukoencephalopathy. Brain stereotactic biopsy at age 16 years demonstrated numerous RFs. With these 2 cases, we review the literature on the various clinico-pathological conditions reported as Alexander's disease. We discuss the nosology of this entity and the pathogeny of RFs formation and dysmyelination. Clues to the diagnosis of this encephalopathy in the living patient are briefly described.
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PMID:Infantile and juvenile presentations of Alexander's disease: a report of two cases. 1010 Sep 59

Darier's disease (DD) is a rare, dominantly inherited disorder that affects the skin producing a variety of types of lesion. Close examination of lesional DD skin shows the presence of abnormal keratinization (epidermal differentiation) and acantholysis (loss of cohesion) of keratinocytes. A number of clinical studies have described the co-occurrence of various neurological and psychiatric symptoms with DD, including mood disorders, epilepsy, mental retardation and a slowly progressive encephalopathy. A single locus for DD has been mapped to chromosome 12q23-q24.1, and a variety of missense, nonsense, frameshift and splicing mutations in the ATP2A2 gene have been described recently in families with DD. This gene encodes the sarcoplasmic/endoplasmic reticulum calcium-pumping ATPase SERCA2, which has a central role in intra-cellular calcium signalling. In this study, we performed mutation analysis on ATP2A2 in 19 unrelated DD patients, of whom 10 had neuropsychiatric phenotypes. We identified and verified 17 novel mutations predicting conservative and non-conservative amino acid changes, potential premature translation terminations and potential altered splicing. Our findings confirm that mutations in ATP2A2 are associated with DD. In neuropsychiatric cases, there was a non-random clustering of mutations in the 3' end of the gene ( P = 0.01), and a predominance of the missense type (70% versus 38% in DD patients). This supports the hypothesis that the DD gene has pleiotropic effects in brain and that mutations in SERCA2 are implicated in the pathogenesis of neuropsychiatric disorders.
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PMID:ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. 1044 25

We present two case reports with severe hypoxic encephalopathy at birth. Studies carried out in the NICU included cranial ultrasonography, CT, and MRI. Due to abnormalities found by the latter two they were referred to our center at the age of two months and one month, and then an early Vojta therapy commenced. Changes were monitored periodically by assessing their spontaneous movements, postural reactions and neurological manifestations. The first case presented with ventricular hemorrhage and was diagnosed as having severe CCD (central coordination disturbance) with the risk of athetotic type cerebral palsy. The second case presented with severe low density in the frontal and temporo-parietal white matter and was diagnosed as having moderate CCD with the risk of mental retardation or brain atrophy. Although their status fluctuated temporarily, the two infants didn't show any paresis or mental retardation. Recently the studies on mechanisms of brain plasticity have advanced. The findings of our experience might suggest that the plasticity of an immature brain could be enhanced by the very early Vojta therapy. We propose that a therapeutic intervention should commence early before clinical symptoms become evident.
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PMID:[Experience of very early Vojta therapy in two infants with severe perinatal hypoxic encephalopathy]. 1056 91

Hallervorden-Spatz disease is a rare, autosomal-recessive hereditary condition characterized by early onset of progressive movement alterations such as dystonia, rigidity, and choreoathetosis, which is usually associated with pyramidal signs and mental deterioration. The authors report two cases for which diagnosis of Hallervorden-Spatz disease was based on clinical manifestations that appeared during the first year of life, illness progression, and late-stage magnetic resonance imaging findings. The possibility that these two cases, along with other previously described rare instances with similar clinical features, be considered as a variant of subtype of the early-onset type of Hallervorden-Spatz disease is suggested. The need to differentiate these cases from cases of static encephalopathy with mental retardation and motor impairment is also stressed.
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PMID:Hallervorden-Spatz disease: two new early childhood onset cases. 1064 7


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