Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain was performed with a 1.5T magnet in 28 patients with unclassified mental retardation (MR) and in 25 age-matched healthy children. Peaks of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), but not of lactate, were observed in both groups on 1H-MRS. In all our subjects of this age range, 1H-MRS revealed an increase with advancing age in the ratio of NAA/Cho (P = .0031), but no developmental change in the NAA/Cr and Cho/Cr ratios. The NAA/Cho ratio was lower in patients with MR than in controls (P = .0016). The NAA/Cr ratio tended to be lower in the MR group, and the Cho/Cr ratio did not differ between patients with MR and controls. These results suggest that in patients with MR, NAA decreases and a disorder and/or dysfunction of neurons in the brain exists.
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PMID:Reduced N-acetylaspartate in the brain observed on in vivo proton magnetic resonance spectroscopy in patients with mental retardation. 855 57

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the central nervous system (CNS) of both DMD children and the mdx mouse model. The underlying biochemical lesion causing mental impairment in DMD is unknown. 1H-magnetic resonance spectroscopy (1H-MRS) detects choline-containing compounds, creatine and N-acetyl aspartate (NAA) in vivo. NAA is commonly used as a chemical marker for neurons, and a decline in NAA is thought to correlate with neuronal loss. Control mice were compared to mdx using a combination of in vivo and in vitro 1H-MRS methods to determine whether neural necrosis or developmental abnormalities occur in dystrophic brain. NAA levels were normal in mdx brain compared to controls suggesting minor, if any, neuronal necrosis in dystrophic brain. In contrast, choline compounds and myo-inositol levels were increased, indicative of gliosis or developmental abnormalities in dystrophic brain.
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PMID:An in vivo and in vitro H-magnetic resonance spectroscopy study of mdx mouse brain: abnormal development or neural necrosis? 888 Jun 86

We performed volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain with a 1.5 T magnet in 28 patients with autism, and compared the results with those from 28 age-matched patients with unclassified mental retardation and 25 age-matched healthy children. Peaks for N-acetylaspartate, choline and creatine, but not lactate, were observed in each group on 1H-MRS. The N-acetylaspartate/choline ratio was lower in patients with mental retardation than in patients with autism and controls (P = .05, respectively). However, there were no differences in the N-acetylaspartate/ choline ratios between patients with autism and controls, and the N-acetylaspartate/creatine and choline/creatine ratios did not differ among the three groups. These results suggest that N-acetylaspartate is decreased in patients with mental retardation and that a disorder or dysfunction of neurons in the brain exists. There also appear to be differences in the brain lesions or dysfunctions found in patients with autism and mental retardation.
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PMID:Differences in brain metabolites between patients with autism and mental retardation as detected by in vivo localized proton magnetic resonance spectroscopy. 907 17

Arginine:glycine amidinotransferase (AGAT, EC 2.1.4.1) deficiency is a recently recognized autosomal recessive inborn error of creatine biosynthesis, characterized by mental retardation and severe language impairment. We extensively investigated a third 5-year-old patient with AGAT deficiency, discovered in the pedigree of the same Italian family as the two index cases. At the age of 2 years he presented with psychomotor and language delay, and autistic-like behavior. Brain MRI was normal, but brain 1H-MRS disclosed brain creatine depletion, which almost completely normalized following creatine monohydrate supplementation. A remarkable clinical improvement paralleled the restoration of brain creatine concentration. AGAT and GAMT (guanidinoacetate:methyltransferase) genes were analyzed in the proband and in 26 relatives, including the two cousins with AGAT deficiency. Sequencing of the proband's AGAT gene disclosed the same homozygous mutation at nt position 9093 converting a tryptophan (TGG) to a stop codon (TAG) at residue 149 (W149X), as already described in the two previously reported cases. The proband's parents and 10 additional subjects of the pedigree were carriers for this mutation. AGAT deficiency was further confirmed by undetectable AGAT activity in the patient's lymphoblasts. Mutation analysis of the GAMT gene revealed a sequence variation in exon 6 (T209M), not in the proband, but in 15 additional subjects from the pedigree. The silent nature of this sequence variation is supported by its homozygosity in one AGAT deficient cousin and in one asymptomatic adult, both with normal GAMT activity.
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PMID:Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. 1246 79

The employment of neuroimaging studies in the evaluation of individuals with developmental delay/mental retardation (DD/MR) is still highly debated. The Consensus Conference of the American College of Medical Genetics has suggested that "neuroimaging appears to have an especially important role in patients with microcephaly or macrocephaly, seizures, loss of psychomotor skills and neurologic signs," whereas the value of neuroimaging investigations "in the normocephalic patient without focal neurological signs is unclear" [Curry et al., 1997]. However, recent literature reports show how the latest neuroimaging techniques (in vivo proton magnetic resonance spectroscopy [H-MRS]) may prove to be useful in the diagnostic process of those individuals with DD/MR and no neurological signs/symptoms. The use of these techniques can, in addition, help in monitoring treatment in distinct metabolic disorders. This review will focus on the usefulness of neuroimaging studies in some of the newer metabolic disorders. This paper will also cover those recognizable patterns of human malformation where neuroimaging findings seem to be relevant both toward diagnosis and management, and add to our understanding of the related behavior phenotype. The essential role of magnetic resonance imaging (MRI) on the progress in the diagnostic recognition of malformations of cerebral cortical development is stressed.
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PMID:Neuroimaging studies in the evaluation of developmental delay/mental retardation. 1256 Oct 55

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by a defect in cholesterol biosynthesis, associated with mental retardation and multisystem structural abnormalities. This study investigated the prevalence of congenital CNS abnormalities by MRI in a large series of patients with SLOS and the correlation of the clinical and biochemical findings with the results of MRI and 1H MRS. Eighteen patients were studied; all underwent MRI of the brain, and 16 had 1H MRS of the cerebral white matter. The ratios choline:NAA, lipid:NAA, and lipid:choline metabolite were found to be correlated with the clinical degree of disease severity, serum total sterol ratios (cholesterol/cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol) and in two cases with the effect of cholesterol therapy. Abnormal CNS findings were noted in five patients, including callosal abnormalities (n = 4), Dandy-Walker variant (n = 1), and arachnoid cyst (n = 1). Holoprosencephaly was noted in one patient with a prevalence of 6%. Choline:NAA was elevated in seven patients. There was a statistically significant positive correlation between the lipid:choline ratio and the serum cholesterol precursor, 8-dehydrocholesterol. In two patients 1H MRS demonstrated abnormally elevated lipids prior to cholesterol therapy, which improved on therapy. The use of MRI and 1H MRS is an effective way to demonstrate brain structural abnormalities in patients with SLOS and may prove to be an effective method for the assessment of the effects of cholesterol replacement therapy in the brain.
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PMID:MRI and 1H MRS findings in Smith-Lemli-Opitz syndrome. 1460 87

The performance of two screening instruments for Pervasive Developmental Disorders was studied in the total population of participants with mental retardation between 4 and 18 years (n = 1059) in Friesland, a northern province of the Netherlands. Parents completed the Autism Behavior Checklist (ABC), staff completed the Scale of Pervasive Developmental Disorder in Mentally Retarded Persons (PDD-MRS). The screening instruments were related to the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule-Generic for 184 participants. The agreement between ABC and PDD-MRS was fair (kappa = .24). The ABC had a better criterion-related validity compared with the Autism Diagnostic Interview-Revised, and the PDD-MRS compared to the Autism Diagnostic Observation Schedule-Generic. However, related to the clinical classification, both instruments performed equally well. Concluding, the ABC and PDD-MRS partially identify the same cases related to external criteria. In addition, each instrument has its own contribution. Both instruments are valuable in detecting children who are at high risk for PDD.
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PMID:Measuring pervasive developmental disorders in children and adolescents with mental retardation: a comparison of two screening instruments used in a study of the total mentally retarded population from a designated area. 1471 29

To date, more than seven families have been reported who carry a mutation in the X-linked creatine-transporter (CrT) gene. The resulting lack of creatine in the brain is associated with mental retardation, severe expressive language disorder, mild epilepsy, and a complete absence of Cr in the brain (measured using MRS). Conversely, these patients had no observable cardiac or musculo-skeletal deficits. In this case study, a 22-year-old patient underwent surgical repair for scoliosis. Proton MRS of this patient's brain demonstrated the near-absence of creatine and phosphocreatine within the cerebral white and deep gray matter structures. Cerebral atrophy was noted with serial MRI examinations. Subsequent genetic and metabolic analysis showed some biochemical anomalies consistent with a CrT deficiency. The mutation in this patient was identified as a deletion at phenylalanine 107 (delF107). Control muscle biopsies were obtained from archived samples, which had been taken with informed consent during routine muscle biopsies for diagnostic purposes. We determined that the total Cr concentration in the skeletal muscle biopsy was 39.3 +/- 2.94 mmol/kg wet wt., which is not significantly different from non-CrT controls, n = 3 (43.3 +/- 3.57 mmol/kg wet wt.). We conclude that the brain appears to lack the ability to transport creatine when there is a mutation in the CrT gene. However, the muscle utilizes another mechanism for maintaining normal creatine levels. Identifying this alternative creatine-transport mechanism may be useful in treating the neurologic and cognitive impairments of patients with creatine-transporter deficiency.
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PMID:Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: a case study. 1553 7

Four Dutch male patients, two brothers from unrelated families were referred for investigation of psychomotor and severe language/speech delay. All four patients showed growth deficiency over the years. Facial features and poor body habitus were quite similar in the patients and in their mothers. Brain MRI showed nonspecific periventricular white matter lesions. In all the patients neuropsychological tests revealed moderate mental retardation, attention deficit and hyperactivity with impulsivity, a semantic-pragmatic language disorder, and oral dyspraxia. This specific cognitive profile is different from other children with mental retardation syndromes and seems to be unique. Excretion of creatine to creatinine ratio in urine of the four boys was increased compared to controls and their creatine uptake in fibroblasts was deficient. In the two brothers from the first pedigree, DNA sequence analysis revealed a novel mutation in the splice donor site in intron 10 (IVS10 + 5G>C, c.1495 + 5G>C) of the SLC6A8 gene leading to skipping of exon 10. In the other sib pair a novel missense mutation (c. 1361C>T; p.Pro544Leu) was found. These are the first families reported, in which the clinical suspicion of a creatine transporter disorder was raised on clinical grounds, before a brain 1H-MRS suggested the diagnosis. Screening of apparently X-linked mental retarded patients with this somatic and behavioral phenotype by the biochemical assay of creatine to creatinine ratio in the urine or DNA sequence analysis of SLC6A8 is worthwhile even when 1H-MRS is not available.
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PMID:Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families. 1569 Mar 73

The Scale of Pervasive Developmental Disorder in Mentally Retarded Persons (PDD-MRS) is described. The PDD-MRS is a simple classification and screening instrument devised for identification of autistic disorders (of the entire spectrum) in persons with mental retardation from mild to profound levels, age-range 2-55 years. The norms of the scale are based on the research protocols of 1230 Dutch persons with mental retardation. The scale's sensitivity for the entire normative sample was found to be 92.4%; calculated separately for persons at all levels of mentally retarded functioning, male and female persons, speaking and non-speaking persons and five age categories, the sensitivity figures range between 87.0 and 100.0%. The specificity of the scale is also 92.4%; for the aforementioned subgroups separately, the specificity figures range between 84.6 and 95.5%. Roughly similar values for sensitivity and specificity were found when using the scale with severely visually impaired/blind persons; severely hearing-impaired/deaf persons; persons with Down syndrome; male persons with fragile X syndrome. The original version of the PDD-MRS dates from 1990; since then the scale has been widely used in the Netherlands and Belgium. The PDD-MRS should be regarded as a useful instrument for identifying PDD in persons with mental retardation.
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PMID:The PDD-MRS: an instrument for identification of autism spectrum disorders in persons with mental retardation. 1613 35


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