Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rett syndrome is a progressive neurological paediatric disorder associated with severe mental deficiency, which affects only girls. The aim of this study was to determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl-cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can explain the clinical manifestation and progression of the disease. Qualitative and quantitative global and regional brain blood flow was evaluated in 12 girls with Rett syndrome and compared with an aged-matched reference group of children. In comparison with the reference group, SPET revealed a considerable global reduction in cerebral perfusion in the groups of girls with Rett syndrome. A large statistical difference was noted, which was more evident when comparing the control group with girls with stage IV Rett syndrome than girls with stage III Rett syndrome. The reduction in cerebral perfusion reflects functional disturbance in the brain of children with Rett syndrome. These data confirm that 99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with Rett syndrome that may be associated with brain atrophy, even when magnetic resonance imaging appears normal.
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PMID:Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD. 925 23

We reported two patients with severe motor and intellectual disabilities syndrome, who were born to mothers having inhaled organic solvents during pregnancy. They had microcephaly, cerebral palsy, mental retardation, seizures, growth failure and minor craniofacial anomalies, variable growth deficiency including a small midface, narrow bifrontal diameter, low-set ears, thin upper lips and micrognathia. Patient 1, a male, died at 8 years and 8 months. The autopsy of his brain revealed marked cerebral atrophy and destruction of bilateral temporal lobes with ventricular enlargements. Microscopic examination revealed migration disorders with polymicrogria at the remaining cerebrum and the cerebellum as well as very thin white matter. Much hemosiderin was found around ventricles, suggesting recurrent minimal bleedings which led to more brain atrophy. Patient 2, a 5 months old male infant, had infantile spasms. On CT and MRI, he had bilateral temporal lobe defect, which might be due to the infarction of bilateral middle cerebral arteries at the prenatal period. These clinical findings are similar to those of other embryopathies, caused by alcohol, phenytoin and other agents. Hersh et al. reported five cases of toluene embryopathy in 1985 and 1988, but they did not report such central nervous system abnormalities. The pathogenesis of toluene embryopathy remains to be solved, but our cases suggested the possible teratogenesis of toluene.
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PMID:[Two cases of toluene embryopathy with severe motor and intellectual disabilities syndrome]. 929 10

Ornithine Transcarbamylase (OTC) is a key urea cycle enzyme. Congenital OTC deficiencies in humans result in hyperammonemia and a spectrum of neurological symptoms including hypotonia, seizures and mental retardation. Neuropathologic evaluation reveals cerebral atrophy, ventricular enlargement and Alzheimer type II astrocytosis. Using an animal model of congenital OTC deficiency, the sparse fur (spf) mouse, recent studies have revealed significant alterations of cholinergic, serotoninergic and glutamatergic neurotransmitter systems. Possible pathophysiologic mechanisms responsible for neuronal cell loss in OTC deficiency include a deficit in cerebral energy metabolism, and glutamate excitotoxicity. Therapy continues to rely on alternative substrate administration including sodium benzoate and sodium phenylacetate. Experimental evidence suggests that acetyl-L-carnitine and glutamate (NMDA) receptor antagonists could be potentially useful therapeutic agents. Liver transplantation is effective in many patients and recent experimental studies using adenoviral vectors suggest that gene therapy may ultimately be useful in the treatment of congenital OTC deficiency.
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PMID:Ornithine transcarbamylase deficiency: pathogenesis of the cerebral disorder and new prospects for therapy. 934 66

A 16-year-old boy with mitochondrial encephalomyopathy had seizures, short stature, muscle weakness, progressive hearing loss, mental retardation, and myoclonus. His cranial computed tomography showed progressive calcification in the basal ganglia and cerebral atrophy. Muscle biopsy revealed many ragged-red fibers with variable cytochrome c oxidase activity and some strongly succinate dehydrogenase-reactive blood vessels. Sequence analysis of the entire mitochondrial DNA revealed a novel point mutation in the tRNA-Thr gene at nucleotide pair 15915. Serum lactate levels were decreased by high-dose coenzyme Q10 (CoQ10) therapy. The spectral power density, a parameter of background activity on electroencephalography, was markedly improved after additional administration of idebenone. After initiation of combined CoQ10 and idebenone therapy, the clinical abnormalities did not progress for 16 months.
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PMID:Mitochondrial encephalomyopathy with 15915 mutation: clinical report. 936 99

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates. However, in the Morris water maze test, a slow worsening of performance could be seen with age. The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities.
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PMID:Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients. 942 33

Congenital ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea cycle enzymes in humans. A large percentage of survivors of neonatal OTC deficiency suffer severe developmental disorders, including seizures, mental retardation and cerebral palsy. Neuropathological studies reveal ventricular enlargement, cerebral atrophy and delayed myelination, as well as Alzheimer type II astrocytosis. Using the sparse-fur (spf) mouse model of congenital OTC deficiency, studies of central cholinergic integrity revealed a developmental delay in choline acetyltransferase activity and of high-affinity [3H]-choline uptake in several brain structures. Subsequent studies of muscarinic cholinergic binding site distribution showed a widespread loss of M1 sites, consistent with cholinergic cell loss. These alterations are similar to those reported in Alzheimer's disease, suggesting that the severe cognitive dysfunction in congenital OTC deficiency may at least partly result from a muscarinic cholinergic lesion. Possible mechanisms involved in the pathogenesis of cholinergic cell loss in congenital OTC deficiency include ammonia-induced inhibition of pyruvate and alpha-oxoglutarate oxidation, resulting in decreased synthesis of acetyl CoA and a cerebral energy deficit, as well as NMDA receptor-mediated excitotoxicity. Treatment of spf mice with acetyl-L-carnitine (ALCAR) results in partial recovery of the developmental choline acetyltransferase deficit, suggesting a potential therapeutic benefit of ALCAR in congenital OTC deficiency. Other therapies currently used include ammonia-lowering strategies (using sodium benzoate or sodium phenylacetate) and, in severe cases, liver transplantation.
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PMID:Evidence for a central cholinergic deficit in congenital ornithine transcarbamylase deficiency. 977 87

Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.
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PMID:Monitoring the CNS pathology in aspartylglucosaminuria mice. 986 38

We report on a 4 year-old girl with a 1p36.3-pter deletion. Clinical findings included minor anomalies of face and distal limbs, patent ductus arteriosus, the Ebstein heart anomaly, and brain atrophy with seizures. Conventional GTG-banded chromosome analysis revealed a normal (46,XX) result. Subsequent analysis by fluorescent in situ hybridization (FISH) using distal probes demonstrated a deletion of 1p36.6-pter. Molecular investigations with microsatellite markers showed hemizygosity at three loci at 1p36.3 with loss of the paternal allele. The deletion of 1p36.3 is difficult to identify by banding alone; indeed, our patient represents the third reported case with a del(1)(p36.3) that was detected only after more detailed analysis. In all three cases the deletion was detected through screening of patients with multiple congenital anomalies/mental retardation syndromes suggestive of autosomal chromosome aberrations for subtelomeric submicroscopic deletions by means of FISH or microsatellite marker analysis. On the basis of these observations we highly recommend that FISH with a subtelomeric 1p probe be routinely performed in patients with similar facial phenotype, severe mental retardation and seizures, and a heart malformation, particularly the Ebstein anomaly.
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PMID:Terminal deletion, del(1)(p36.3), detected through screening for terminal deletions in patients with unclassified malformation syndromes. 1056 88

We report on a family with severe X-linked mental retardation (XLMR) and progressive, severe central nervous system deterioration. Three of the five affected males died of secondary complications before the age of 10 years and none have survived past the age of 10. These complications included swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections. In addition, hypotonia and a mild myopathy were also present. All had a characteristic facies, including downslanting palpebral fissures, hypertelorism, and a short nose with a low nasal bridge. The two older boys showed cerebral atrophy by CT. No metabolic abnormalities were identified. Three obligate carriers had an IQ less than 80. The causal gene has been localized distal to DXS8103 in Xq28, a region spanning 5cM. No other XLMR disorder with these manifestations have been localized to this region and this appears to be a new disorder.
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PMID:XLMR syndrome characterized by multiple respiratory infections, hypertelorism, severe CNS deterioration and early death localizes to distal Xq28. 1039 36

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


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