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)

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency, inherited as an autosomal recessive trait, is the most prevalent inborn error of methionine metabolism. Its diverse clinical expression may include ectopia lentis, skeletal abnormalities, mental retardation, and premature arteriosclerosis and thrombosis. This variability is likely caused by considerable genetic heterogeneity. We investigated the molecular basis of CBS deficiency in 29 Dutch patients from 21 unrelated pedigrees and studied the possibility of a genotype-phenotype relationship with regard to biochemical and clinical expression and response to homocysteine-lowering treatment. Clinical symptoms and biochemical parameters were recorded at diagnosis and during long-term follow-up. Of 10 different mutations detected in the CBS gene, 833T-->C (I278T) was predominant, present in 23 (55%) of 42 independent alleles. At diagnosis, homozygotes for this mutation (n=12) tended to have higher homocysteine levels than those seen in patients with other genotypes (n=17), but similar clinical manifestations. During follow-up, I278T homozygotes responded more efficiently to homocysteine-lowering treatment. After 378 patient-years of treatment, only 2 vascular events were recorded; without treatment, at least 30 would have been expected (P<.01). This intervention in Dutch patients significantly reduces the risk of cardiovascular disease and other sequelae of classical homocystinuria syndrome.
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PMID:The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment. 1036 17

Supravalvular aortic stenosis is a rare cause of left ventricular outflow obstruction in adults. It occurs as an isolated defect sporadically or on a hereditary basis with an autosomal dominant trait without further phenotypical anomalies, or as part of the Williams syndrome with mental retardation and multiple other anomalies. This lesion was proved to result from a defect of the elastin coding gene. Supravalvular aortic stenosis is frequently associated with cardiovascular defects, particularly of the peripheral pulmonary arteries, thoracic aorta, carotid, subclavian, and coronary arteries and the aortic valve. The coronary arteries are subject to an increased perfusion pressure leading to dilatation, tortuosity and accelerated arteriosclerosis. We give details of a 35-year-old patient in whom a previously asymptomatic supravalvular aortic stenosis is associated with an excessive dilatation of the right coronary artery and the left anterior descending coronary artery as well as an ostium stenosis of the left common carotid artery. The patient did not present any phenotypical anomalies of the Williams syndrome.
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PMID:[Congenital tubular supravalvular aortic stenosis with massive coronary artery dilatation in a 35-year-old man]. 1079 76

The article summarizes the 3-year (1998-2000) consulting and treatment experience of a psychotherapeutic unit in one Moscow general hospital. Psychiatrists realized emergent and planned consultations of the mentally-ill patients in all hospital departments, conducted, in addition to general treatment, psychopharmacotherapy and psychotherapy or directed them, on demand, to psychiatric hospitals. For the 3-year period, the psychiatrists have consulted 4685 somatic patients with comorbid mental diseases (5% of the total amount of the patients admitted to the hospital at that period), 1360 patients (29%) being affected with psychotic disorders. One hundred eighty two patients were diagnosed to have schizophrenia, 784--arteriosclerosis and old-age psychosis and dementia, 45--reactive psychosis, 16--epilepsy (disphoria and psychotic episodes), 67--mental retardation with inadequate behavior, 266--delirium of alcoholic and drug addiction genesis. In some cases, usage of psychotropics, in combination with psychotherapy, has resulted in recovery or considerable psychic state improvement in 9.1% of the patients, improvement in 52% ones, insignificant improvement in 36%. In 2.9% of the cases, the effect of treatment has not been achieved.
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PMID:[Psychiatric service in general hospital]. 1191 10

Cystathionine beta-synthase (CBS) deficiency is a rare autosomal recessive disorder that is the most frequent cause of clinical homocystinuria. Patients not treated in infancy have multi-systems disorders including dislocated lenses, mental deficiency, osteoporosis, premature arteriosclerosis, and thrombosis. In this paper, we examine the relationship of the clinical and biochemical phenotypes with the genotypes of 12 CBS deficient patients from 11 families from the state of Georgia, USA. By DNA sequencing of all of the coding exons we identified mutations in the CBS genes in 21 of the 22 possible mutant alleles. Ten different missense mutations were identified and one novel splice-site mutation was found. Five of the missense mutations were previously described (G307S, I278T, V320A, T353M, and L101P), while five were novel (A226T, N228S, A231L, D376N, Q526K). Each missense mutation was tested for function by expression in S. cerevisiae and all were found to cause decreased growth rate and to have significantly decreased levels of CBS enzyme activity. The I278T and T353M mutations accounted for 45% of the mutant alleles in this patient cohort. The T353M mutation, found exclusively in four African American patients, was associated with a B(6)-nonresponsive phenotype and detection by newborn screening for hypermethioninemia. The I278T mutation was found exclusively in Caucasian patients and was associated with a B(6)-responsive phenotype. We conclude that these two mutations occurred after ethnic socialization and that the CBS genotype is predictive of phenotype.
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PMID:Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype. 1463 2

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