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)

Some hitherto undetected differences in chemical and macromolecular structure between both dermatan sulphates and heparan sulphates excreted in the Hurler and Hunter syndromes are demonstrated. 1. Of Hunter dermatan sulphate, 37-43% is resistant to periodate oxidation, as opposed to 25% of the corresponding Hurler material. It is likely that the resistance is conferred by the presence of sulphate groups on carbon atoms 2 or 3 of the iduronate residues, correlating with the recently established deficiency of a sulphoiduronate sulphatase in Hunter fibroblasts. 2. Two distinct electrophoretic species of dermatan sulphate are found in Hunter urine, but only one in Hurler preparations. 3. Ion-exchange chromatography and gel filtration reveal that Hurler dermatan sulphate is more heterogeneous with respect to molecular weight distribution than the other. The dermatan sulphates were degraded by hyaluronidase to a limited extent. 4. Hurler heparan sulphate contains a higher proportion of sulphoamino-glucose than material from Hunter urine. Similar high levels in Sanfilippo patients, representing 65-78% of the total glucosamine suggest a direct correlation with mental deficiency.
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PMID:Comparative structural studies of urinary glycosaminoglycans in the Hurler and Hunter syndromes. 12 16

A particular sibship, with mild and severe types of Sanfilippo B disease within the same family, was re-examined after 12 years. The phenotypes of the mild and of the severe patients were maintained, specifically the mental retardation. Cultures of lymphoblasts from the mild patient were established and proteins were electrophoresed in native conditions and then immunoblotted with specific antibody. Two bands of 182,000 and 131,000 Da were found, comigrating with the enzyme from normal lymphoblasts and the enzyme from normal urine. The data are discussed in relationship to the molecular defect underlying alpha-N-acetylglucosaminidase deficiency and to the ability of the antiserum to react with normal, mutant, monomeric and multimeric forms of the enzyme.
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PMID:Sanfilippo B disease: a re-examination of a particular sibship after 12 years. 190 36

MR imaging of the brain was performed in eight patients with mucopolysaccharidosis (MPS). Two had MPS I S, one had MPS IIA, two had MPS IIB, two had MPS IIIB, and one had MPS VI. In the patients with MPS IIA and MPS VI, T1 and T2 were prolonged in various areas of the cerebral white matter. These findings seemed to correspond with the development of pathologic changes in MPS, such as perivascular pits in the white matter observed on slices of the fixed brain. In the patients with MPS IIA and MPS IIIB, the white matter did not show the proper signal intensity, which suggested that myelination was insufficient and that infiltration or deposition of glycosaminoglycan had occurred; this was consistent with the association of these two types with mental retardation. In the patients with MPS I S, no intracranial abnormalities were detected on MR images. MR imaging of the brain may be used to obtain a differential diagnosis of the various types of MPS, to estimate the extent of mental retardation, and to monitor the progress of this disease.
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PMID:MR imaging of the brain in patients with mucopolysaccharidosis. 255 7

Two sisters are described with mucopolysaccharidosis (MPS) Sanfilippo type C syndrome. This diagnosis is emphasized to be easily overlooked due to subtile clinical and radiological deviations, but should be considered in any case of unspecific progressive mental retardation, especially when sleep disturbance, aggressivity and hyperactivity are prominent symptoms.
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PMID:Sanfilippo type C syndrome in two sisters. 392 Aug 64

Mucopolysaccharidosis (MPS) includes a group of lysosomal storage diseases. Among them, type III (Sanfilippo) disease is rarely described in Taiwan because of their complexity. With accurate quantifying and precise separation of urinary glycosaminoglycans (GAGs), and specific enzyme measurements, two cases of MPS IIIB disease were able to be described. They both had mild-to-moderate degrees of mental retardation, facial dysmorphism and dysostosis multiplex which do not differ from other types of MPS. Total amounts of GAGs in the urine were only mildly elevated but, among them, heparan sulfate was the highest. Skin fibroblasts alpha-N-acetyl-glucosaminidase activities were low in both cases. Therefore, analysis of GAGs and enzyme assays are important for the diagnosis of patients suspected to have MPS, especially type III disease.
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PMID:Diagnosis of mucopolysaccharidosis type IIIB. 894 24

Sanfilippo syndrome type B or mucopolysaccharidosis type IIIB (MPS IIIB) is one of a group of lysosomal storage disorders that are characterised by the inability to breakdown heparan sulphate. In MPS IIIB, there is a deficiency in the enzyme alpha-N-acetylglucosaminidase (NAGLU) and early clinical symptoms include aggressive behaviour and hyperactivity followed by progressive mental retardation. The disease is autosomal recessive and the gene for NAGLU, which is situated on chromosome 17q21, is approximately 8.5 kb in length and contains six exons. Primers were designed to amplify the entire coding region and intron/exon boundaries of the NAGLU gene in 10 fragments. The PCR products were analysed for sequence changes using SSCP analysis and fluorescent DNA sequencing technology. Sixteen different putative mutations were detected in DNA from 14 MPS IIIB patients, 12 of which have not been found previously. The mutations include four deletions (219-237del19, 334-358del25, 1335delC, 2099delA), two insertions (1447-1448insT, 1932-1933insGCTAC), two nonsense mutations (R297X, R626X), and eight missense mutations (F48C, Y140C, R234C, W268R, P521L, R565W, L591P, E705K). In this study, the Y140C, R297X, and R626X mutations were all found in more than one patient and together accounted for 25% of mutant alleles.
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PMID:Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB). 983 37

The Sanfilippo type A syndrome, one of the most frequent forms of mucopolysaccharidosis III, is characterized by severe mental retardation, progressive neurological degeneration, and mild somatic changes. It is due to a deficiency of heparan-N-sulfatase (sulfamidase) activity and consequent excretion of heparan sulfate in the urine. The disease is transmitted through an autosomal recessive mechanism, and more than 60 gene mutations have been identified. Up to now, only 10 cases of attenuated form of Sanfilippo type A syndrome have been described, and the specific mutation has been identified only in two of them. We report here on a female patient, 20 years old, with Sanfilippo type A syndrome presenting with a mild clinical phenotype characterized essentially by a moderate nonevolving mental retardation. The genetic analysis demonstrated that the patient is homozygous for mutation R206P; presence of polymorphism R456H was also found. This study places R206P as a mild mutation underlying Sanfilippo type A disease.
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PMID:An adult Sanfilippo type A patient with homozygous mutation R206P in the sulfamidase gene. 1563 19

Sanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N-acetyl-alpha-D-glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18-63 years old. Apart from the youngest, they had lost mobility at 36-68 years. Most had developed physical problems, in particular in the 4th-6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS.
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PMID:Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems? 1764 47

Mucopolysaccharidosis type IIIB (Sanfilippo syndrome) is a lysosomal storage disease caused by a genetic defect in the production of alpha-N-acetylglucosaminidase. This results in lysosomal and extracellular accumulation of the undegraded glycosaminoglycan (GAG) substrate, heparan sulphate. Affected patients show progressive CNS degeneration characterised by mental retardation, hyperactivity and seizures, with death usually in the mid teens to early twenties. Visceral organ storage is also present but is relatively mild compared to other MPS diseases storing similar substrates. No treatments currently exist for MPS IIIB. Genistein is a broad spectrum protein tyrosine kinase inhibitor which acts on several different growth factor receptors, notably EGF and IGF receptors, both of which are important for proteoglycan synthesis. Recent work has shown that genistein can reduce GAG synthesis in patients' fibroblasts in vitro and there is evidence in patients to suggest that it may be an effective substrate reduction therapy agent for MPS III. Here we have tested the dose responses of MPS IIIB mice to daily sub-chronic dosing of genistein in half log increments compared to carrier over 8 weeks. We show clear reductions in liver lysosome compartment size in both sexes and significant dose dependent improvements in total liver GAGs and hair morphology in male MPS IIIB animals following genistein treatment. Male MPS IIIB mice exhibited considerably more liver storage than females and responded better to treatment. No changes in total GAGs, lysosomal size or reactive astrogliosis in the brain cortex were observed after 8 weeks of treatment despite evidence that genistein can cross the blood brain barrier. This is the first demonstration of genistein treatment in MPS models in vivo.
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PMID:Genistein reduces lysosomal storage in peripheral tissues of mucopolysaccharide IIIB mice. 1963 71

Mucopolysaccharidoses are autosomal and recessive lysosomal storage disorders caused by the deficiency of a lysosomal enzyme involved in glycosaminoglycan catabolism. The Sanfilippo type A disease (MPS III A) results from sulfamidase deficiency, which leads to accumulation of heparan sulfate, whereas Sly disease (MPS VII) results from beta-glucuronidase deficiency, leading to accumulation of heparan, dermatan, and chondroitin sulfates. These syndromes are characterized by severe central nervous system degeneration, resulting in progressive mental retardation, and fatality occurs in severely affected children. To date, no effective treatment is available except for bone marrow transplantation in specific cases. Recently, the use of genistein, an isoflavone that inhibits glycosaminoglycans synthesis, has been tested as substrate reduction therapy for neuronopathic forms of these diseases.We tested five natural analogs to genistein in human fibroblasts from both Sanfilippo A and Sly patients. Four molecules were as efficient as genistein in decreasing glycosaminoglycan accumulation. Moreover, a combination of several isoflavones was more efficient than one single isoflavone, suggesting a synergistic effect. These preliminary data may offer new perspectives for treating Sly and Sanfilippo A diseases and could be relevant to other neurological forms of mucopolysaccharidoses.
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PMID:Storage correction in cells of patients suffering from mucopolysaccharidoses types IIIA and VII after treatment with genistein and other isoflavones. 2008 60


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