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

The metabolic and anatomical substrate of most forms of mental retardation is not known. Because the basis of normal brain function is not sufficiently understood, the basis of abnormal function is understood poorly. Even in disorders where the fundamental biochemical defect is known, such as phenylketonuria (PKU) and other enzyme defects, the exact basis for brain dysfunction is uncertain. The outcome for treated PKU, galactosemia, homocystinuria, and lysosomal disorders is not yet optimal. The various forms of nonketotic hyperglycinemia often respond poorly to current therapy. Less familiar disorders, with or without seizures, such as deficient synthesis of serine or creatine and impaired glucose transport into the brain, and disorders with variable malformations, such as Smith-Lemli-Opitz (SLO) syndrome and the congenital disorders of glycosylation (CDGs), may initially be thought to be a nonspecific form of developmental delay. Less familiar disorders, with or without seizures and disorders with variable malformations may initially be thought to be a nonspecific form of developmental delay. Simple tests of urine, blood, and cerebrospinal fluid may lead to a diagnosis, accurate genetic counseling, and better treatment. Metabolic brain imaging (magnetic resonance spectroscopy (MRS)) has also helped to reveal biochemical abnormalities within the brain.
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PMID:Metabolic disorders and mental retardation. 1256 Oct 56

Homocystinuria usually presents with ectopia lentis, mental retardation, thromboembolic complications, and skeletal abnormalities. Whereas neuropsychiatric abnormalities are often recognized in untreated homocystinuria, initial presentation with acute psychosis has only rarely been reported. We describe a previously well 17-year-old adolescent with an acute psychosis characterized by auditory and visual hallucinations and marked paranoia who was found to have pyridoxine-responsive homocystinuria. His mental state normalized within several weeks of inception of pyridoxine and antipsychotic therapy. Pyridoxine-responsive homocystinuria is commonly missed on neonatal screens and should be recognized as a potentially treatable cause of acute psychosis in childhood and adolescence.
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PMID:Homocystinuria presenting as psychosis in an adolescent. 1258 32

A group of 28 patients with inherited metabolic disease (homocystinuria galactosaemia, maple syrup urine disease and biotinidase deficiency) diagnosed by screening were compared with a group of 17 similar patients identified clinically. The rate of hospitalization was similar for the two groups. The patients diagnosed clinically showed a higher incidence of mental retardation and their parents experienced greater stress and found greater difficulty in meeting their child's needs.
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PMID:Newborn screening compared to clinical identification of biochemical genetic disorders. 1263 45

Homocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine (Hcy). Mental retardation, ischemia and other neurological features, whose mechanisms are still obscure are common symptoms in homocystinuric patients. In this work, we investigated the effect of Hcy administration in Wistar rats on some parameters of energy metabolism in the hippocampus, a cerebral structure directly involved with cognition. The parameters utilized were 14CO2 production, glucose uptake, lactate release and the activities of succinate dehydrogenase and cytochrome c oxidase (COX). Chronic hyperhomocysteinemia was induced by subcutaneous administration of Hcy twice a day from the 6th to the 28th day of life in doses previously determined in our laboratory. Control rats received saline in the same volumes. Rats were killed 12 h after the last injection. Results showed that Hcy administration significantly diminished 14CO2 production and glucose uptake, as well as succinate dehydrogenase and COX activities. It is suggested that impairment of brain energy metabolism may be related to the neurological symptoms present in homocystinuric patients.
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PMID:Impairment of energy metabolism in hippocampus of rats subjected to chemically-induced hyperhomocysteinemia. 1269 99

Two Korean sisters, one detected during neonatal screening, the other ascertained at age 3 years during family screening, have persistent hypermethioninaemia without elevation of plasma tyrosine or severe liver disease. Plasma total homocysteine (tHcy) is mildly elevated, but not so markedly as to establish a diagnosis of homocystinuria due to cystathionine beta-synthase (CBS) deficiency. CBS deficiency was ruled out by the presence of slightly elevated concentrations of plasma cystathionine. Although the plasma concentrations of methionine were markedly elevated, plasma S-adenosylmethionine (AdoMet) was not. This pattern of metabolic abnormalities suggested that the patients have deficient activity of methionine adenosyltransferase (MAT) in their livers (MAT I/III deficiency). Molecular genetic studies demonstrate that each patient is a compound heterozygote for two mutations in MAT1A, the gene that encodes the catalytic subunit that composes MAT I and MAT III: a previously known inactivating G378S point mutation, and a novel W387X truncating mutation. W387X mutant protein, expressed in E. coli and purified, has about 75% of wild-type activity. Negative subunit interaction between the mutant subunits is suggested to explain the hypermethioninaemia of these sisters. They have had normal growth and development and have no mental retardation, neurological abnormalities, or other clinical problems. They are the first individuals of Korean descent proven to have MAT I/III deficiency.
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PMID:Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation. 1270 96

The authors present the case of a 25-year-old female patient, white, with mental retardation and proptosis, and a history of repeated cerebrovascular events. During investigation elevated levels of homocysteinemia and homocystinuria were demonstrated. The authors present a review of related literature.
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PMID:Hyperhomocysteinemia--case report. 1276 2

Homocystinuria is an inherited metabolic disease characterized biochemically by increased blood and brain levels of homocysteine caused by severe deficiency of cystathionine beta-synthase activity. Affected patients present mental retardation, seizures, and atherosclerosis. Oxidative stress plays an important role in the pathogenesis of many neurodegenerative and vascular diseases, such Alzheimer's disease, stroke, and atherosclerosis. However, the mechanisms underlying the neurological damage characteristic of homocystinuria are still poorly understood. To evaluate the involvement of oxidative stress on the neurological dysfunction present in homocystinuria, we measured thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and total radical-trapping antioxidant potential (TRAP) and antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) in rat hippocampus in the absence (controls) or in the presence of homocysteine (10-500 microM) in vitro. We demonstrated that homocysteine significantly increases TBARS and decreases TRAP, both in a dose-dependent manner, but did not change antioxidant enzymes. Our results suggest that oxidative stress is involved in the neurological dysfunction of homocystinuria. However, further studies are necessary to confirm and extend our findings to the human condition and also to determine whether antioxidant therapy may be of benefit to these patients.
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PMID:In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. 1282 33

Homocystinuria due to cystathionine beta-synthase deficiency is the second most treatable aminoacidopathy. The reported incidence varies from 1 in 344,000 worldwide to 1 in 65,000 in Ireland. Untreated patients with homocystinuria have severe hyperhomocysteinaemia. Amongst its pathological sequelae, which include mental retardation, ectopia lentis and osteoporosis, vascular events remain the major cause of morbidity and mortality in untreated patients. Recognized modalities of treatment include pyridoxine, in combination with folic acid and vitamin B12; methionine-restricted, cystine-supplemented diet; and betaine. The natural history of vascular events is such that half will have an event before age 30 years and there is a predicted one event per 25 years at the time of maximal risk. In 158 patients with 2822 patient-years of treatment, there would be a predicted 112 events if left untreated, but instead only 17 vascular events were recorded during treatment (relative risk 0.09, 95% CI 0.036 to 0.228; p < 0.0001). Appropriate chronic treatment to lower hyperhomocysteinaemia is effective in reducing the potentially life-threatening vascular risk in patients with homocystinuria. These findings may also have relevance to the significance of mild hyperhomocysteinaemia that is commonly found in patients with premature vascular disease.
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PMID:Classical homocystinuria: vascular risk and its prevention. 1288 65

Homocystinuria is an autosomal recessive disorder of methionine metabolism due to cystathionine B-synthetase deficiency. It is the second most common inborn error of amino acid metabolism after phenylketonuria. In addition to the eyes, the skeletal, central nervous and vascular systems are usually affected by homocystinuria. We report two family cases of two sisters and two brothers with homocystinuria revealed by lenticular dislocation into the anterior chamber, associated with mental and growth retardation, and an isolated case of homocystinuria revealed by poor vision with Marfan syndrome and mental retardation. They all underwent surgical lensectomy with anterior vitrectomy under general anesthesia with anaesthesic precautions to prevent vascular thrombosis. Ocular complications are common in patients with homocystinuria. Treatment must include dietary changes to reduce the incidence of ectopia lentis and mental retardation. Surgical treatment with modern microsurgical techniques should be considered in advanced ocular manifestations of homocystinuria.
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PMID:[Ocular and systemic complications of homocystinuria: a report of five cases]. 1469 98

Within the past four decades, the efforts of investigators worldwide have established the amino acid homocysteine as an important factor in arteriosclerosis and diseases of aging. After its discovery in 1932, homocysteine was demonstrated to be an important intermediate in the metabolism of amino acids. However, little was known about the broader biomedical significance of homocysteine until 1962, when children with mental retardation, accelerated growth, dislocated ocular lenses, and frequent vascular thrombosis were found to excrete homocysteine in the urine. My study of two patients with homocystinuria caused by different inherited enzymatic disorders in 1968 disclosed advanced widespread arteriosclerotic plaques in both cases. This discovery led to the conclusion that homocysteine causes vascular disease by a direct effect on the cells and tissues of the arteries. This interpretation suggests that homocysteine is important in the pathogenesis of arteriosclerosis in persons with hereditary, dietary, environmental, hormonal, metabolic, and other factors predisposing them to hyperhomocysteinemia. Within the past decade, many major clinical and epidemiological studies have proven that hyperhomocysteinemia is a potent independent risk factor for vascular disease. According to the homocysteine theory of arteriosclerosis, insufficient dietary intake of the B vitamins, folic acid and pyridoxine, caused by losses of these nutrients during processing of foods, leads to elevation of blood homocysteine and vascular disease in the general population. The dramatic decline in cardiovascular mortality since the 1960s in the United States is attributed to fortification of the food supply by synthetic pyridoxine and folic acid. The recent Swiss Heart Study showed that B vitamins slowed restenosis in patients with coronary arteriosclerosis treated with angioplasty. Currently, more than 20 prospective, worldwide, interventional trials involving at least 100,000 participants are examining whether lowering plasma homocysteine levels with supplemental B vitamins will prevent mortality and morbidity from arteriosclerotic vascular disease.
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PMID:Homocysteine, vitamins, and prevention of vascular disease. 1513 38


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