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)

Methemoglobinemia and mental retardation associated with NADH-diaphorase deficiency was found in a 2-year-old girl of Spanish origin. She showed no NADH-diaphorase activity in either erythrocytes or leukocytes, but electrophoretic studies of the hemolysate showed traces of an enzyme with normal mobility. Cytochrome b5 reductase activity was also found to be absent in the leukocytes of the propostius. Intermediate NADH-diaphorase activity was found in erythrocytes and leukocytes in her parents and her sister in accordance with the autosomal recessive mode of inheritance of this enzymopathy. The relationship between a generalized cytochrome b5 reductase deficiency and the progressive neurological involvement in our patient is discussed briefly.
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PMID:Congenital methemoglobin-reductase (cytochrome b5 reductase) deficiency associated with mental retardation in a Spanish girl. 9 93

In congenital methemoglobinemia associated with mental retardation a generalized deficiency of NADH-cytochrome beta 5 reductase (NADH : ferricytochrome beta 5 oxidoreductase, EC 1.6.2.2) has been found in soluble extracts of red blood cells, as well as in deoxycholate-treated extracts of leukocytes, muscle, liver and fibroblasts (Leroux et al. (1975) Nature 258, 619-620). In the present study the relationship between the microsomal (I) and the soluble (II) NADH-cytochrome beta 5 reductase was investigated, using human placenta as a source of enzyme. Both forms were compared to the human red-cell soluble NADH-methemoglobin reductase (III) and NADH-cytochrome beta 5 reductase (IV). The four entities exhibited great immunological similarities. It is concluded that the three soluble enzymes (II, III and IV) are identical. The detergent-solubilized microsomal NADH-cytochrome beta 5 reductase (I) is immunologically very similar to the soluble enzymes, but presents distinct features possibly due to the presence of a hydrophobic part.
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PMID:Soluble and microsomal forms of NADH-cytochrome beta 5 reductase from human placenta. Similarity with NADH-methemoglobin reductase from human erythrocytes. 40 44

Effect of the deficiency of NADH-cytochrome b5 reductase on fatty acid elongation was studied in the platelets and leukocytes taken from a patient of hereditary methemoglobinemia associated with mental retardation. The activity of fatty acid elongation was determined by measuring the incorporation of [2-14C]malonyl-CoA into palmitoyl-CoA. The de novo biosynthesis of fatty acids was blocked by the addition of phosphotransacetylase, and the elongation system could be assayed in the homogenates separated from de novo biosynthesis. As compared to normal subjects approximately 40% decrease of fatty acid elongation was observed both in the platelets and leukocytes from the patient.
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PMID:Decrease of palmitoyl-CoA elongation in platelets and leukocytes in the patient of hereditary methemoglobinemia associated with mental retardation. 367 85

Recessive congenital methemoglobinemia (RCM) is due to the homozygous deficiency of NADH-cytochrome b5 reductase (EC 1.6.2.2.). In type I disease, in which the patients are only methemoglobinemic, the enzyme defect is fully expressed in the erythrocytes, whereas the leukocytes are much less affected. In type II disease, in which the patients are, in addition, mentally retarded, the defect is generalized to all the tissues including cultured fibroblasts. In the present study we have investigated Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL) derived from patients with both types of cytochrome b5 reductase deficiency and from nondeficient individuals. The total cytochrome b5 reductase activity of the control LCL was found to be similar whatever the LCL origin, except for one lymphoma line (Daudi). The enzyme from the control LCL (c 252/B 95) was found to be immunologically related to the human soluble erythrocyte cytochrome b5 reductase, indicating that it is the product of the same gene: the DIA1 (diaphorase) locus. The LCL derived from one patient with the type I disease and two patients with the type II disease were investigated.l In the former the defect was expressed to a lesser degree than in the cases with mental retardation in which the defect was much pronounced, and involved both the mitochondrial and the microsomal fraction. This indicated that all the subcellular forms of the cytochrome b5 reductase are under the same genetic control. Altogether, these data show that the LCL are a favorable material for studying both types of cytochrome b5 reductase deficiency and for investigating in depth the molecular aspects of this metabolic disease.
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PMID:NADH cytochrome b5 reductase activity in lymphoid cell lines. Expression of the defect in epstein Barr virus transformed lymphoblastoid cell lines from patients with recessive congenital methemoglobinemia. 626 99

The fatty acid composition of the triglyceride in adipose tissue in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation was analyzed and compared with age-matched controls. The proportions of linoleic acid, linolenic acid and arachidonic acid were decreased to less than half of normal level. There was a decrease in total unsaturated fatty acids and an increase in palmitic acid. These results revealed an undeveloped pattern of fatty acid composition in adipose tissue in the patient.
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PMID:Adipose fatty acid composition in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation. 663 38

The lipid compositions of liver, kidney, spleen and muscle in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation were analyzed and compared with age-matched controls. The contents of cholesterol and phospholipids (mumol/g) in each organ were within the normal range. Diminished proportions of unsaturated fatty acids were observed in ethanolamine phosphoglycerides (EPG) of the liver. The proportion of linoleic acid decreased to less than half of the normal level in EPG of liver, kidney and spleen.
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PMID:Lipids of liver, kidney, spleen and muscle in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation. 670 47

Normal levels of NADH-cytochrome b5 reductase activity in platelets, lymphocytes and granulocytes were determined. The homogenate of each cell was treated with Triton X-100 after incubation with lipoprotein lipase. The reductase was extracted very well from the cells by this treatment. Moreover, the assay of the reductase activity in the cells became accurate and reproducible by the treatment. The reductase level of each cell was also determined in cases of hereditary methemoglobinemia. It was normal in the case of the disease without mental retardation, and low with mental retardation. This latter case might be due to the deficiency of cytochrome b5 reductase in the whole tissue.
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PMID:NADH-cytochrome b5 reductase in platelets and leukocytes with special reference to normal levels and to levels in carriers of hereditary methemoglobinemia with or without neurological symptoms. 676 12

Prenatal diagnosis of congential enzymopenic methaemoglobinaemia (CEM) with mental retardation was performed in two fetuses at risk for generalized NADH-cytochrome b5 reductase deficiency. In the first case the enzyme activity of cultured amniotic cells was in the heterozygous to normal range. The mother delivered a normal baby with normal enzyme activity in cord blood cells. In the second case, the amniotic cells were almost completely enzyme deficient. The pregnancy was terminated, and the diagnosis of homozygous NADH-cytochrome b5 reductase deficiency was confirmed in cord blood cells, in several different tissues and in cultured fibroblasts from the aborted fetus.
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PMID:Prenatal diagnosis of congenital enzymopenic methaemoglobinaemia with mental retardation due to generalized cytochrome b5 reductase deficiency: first report of two cases. 734 9

The lipid classes and fatty acid compositions of myelin, white matter and gray matter were analyzed in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation. When compared with normal data, the percentage of 24:1 was considerably decreased and diminished unsaturation was observed in cerebrosides, whereas the sum of 24:0 and 24:1 was the same as in normals. The ratio of hydroxy fatty acids to total fatty acids in cerebrosides was low. The contents of cholesterol and phospholipids in white matter were reduced to 80% of the normal, whereas cerebroside was reduced to 48% of the normal.
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PMID:Lipids of myelin, white matter and gray matter in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation. 737 82

In order to understand the mechanisms responsible for the generation of different isoforms (membrane-bound and soluble) of NADH-cytochrome b5 reductase, and the different clinical forms of recessive congenital methemoglobinemia due to the deficiency of this enzyme in humans (type I, without mental retardation; type II, with mental retardation), we have looked for mRNA heterogeneity in various rat tissues. We have found four types of mRNAs, each with a different first exon (1L, 1R, 1X and 1Y), all of which were precisely spliced to join the common second exon. Our results are consistent with a 5'-->3' 'scanning' mechanism for splice-site selection. The previously characterized 1L and 1R transcripts arise from the alternative use of either a ubiquitous promoter (Pr-L) or an erythroid-specific promoter (Pr-R). In addition, the X and Y RNA species are novel transcripts which are expressed ubiquitously and at a relatively low level. The first alternative exons 1X and 1Y are noncoding, such that the AUG codon present in the common second exon is functional, as it is in the R mRNA. Thus, the X and Y mRNAs are expected to be translated in vivo into a ubiquitous soluble enzyme. Consequently, the rat NADH-cytochrome-b5-reductase gene is expressed through the use of at least four different promoters, which are probably subjected to different forms of regulation. This model of gene expression in rat could be important in understanding the basis for the different types of the NADH-cytochrome-b5-reductase enzyme and their deficiency in man.
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PMID:Heterogeneity of the rat NADH-cytochrome-b5-reductase transcripts resulting from multiple alternative first exons. 814 27


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