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)

Mucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.
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PMID:Mental retardation in mucopolysaccharidoses correlates with high molecular weight urinary heparan sulphate derived glucosamine. 2601 23

Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder). This data indicates many large animal disorders which can be models to examine the above human mental and behavioral disorders.
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PMID:Large animals as potential models of human mental and behavioral disorders. 2943

We herein report anesthetic management during aortic valve replacement for aortic valve regurgitation in a patient with adult mucopolysaccharidosis type II (MPS type 2) (Hunter syndrome). This disorder is rare and related to the accumulation of a mucopolysaccharide in lysosomes. It affects various organs, including the airways, heart, and central nerves. In children with MPS type 2, the risk of airway obstruction during anesthesia/sedation is high, and the degree of difficulty increases with aging. The patient described herein was a 33-year-old male without mental retardation. Before surgery, trismus, megaloglossia, and the disturbance of cervical vertebral excursion were noted, suggesting difficulties with ventilation/intubation. Anesthesia was induced under sedation/spontaneous respiration. A laryngeal deployment was conducted using a video laryngoscope; however, the Cormack grade was III. Nasotracheal fiber intubation was performed, and airway obstruction occurred. A muscle relaxant was administered, facilitating ventilation. However, subglottic stenosis, which was not detected before the surgery, made the tracheal tube insertion difficult. Aortic valve replacement was performed without complications. A detailed postoperative examination of the airways revealed oropharyngeal soft tissue outgrowth, narrowing of the upper airway, subglottic stenosis, and displacement/circumflex of the airway axis. Either awake intubation or rapid induction can be selected for this patient; however, either way have risks of airway obstruction. It is important that strategies under light anesthesia or incomplete neuromuscular blockade should be avoided for such our patient as suggested in the JSA airway management guidelines. A preoperative multidisciplinary airway assessment and simulation are important.
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PMID:Perioperative airway management for aortic valve replacement in an adult with mucopolysaccharidosis type II (Hunter syndrome). 2952 52

Mucopolysaccharidosis type II (Hunter syndrome) is a lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase leading to tissue accumulation of glycosaminoglycans. It manifests with short stature, joint stiffness, coarse facial features, hepatosplenomegaly, and progressive mental retardation. Most children die in the first or second decade from pulmonary or cardiac involvement. Until recently, no specific treatment was available. A Phase II/III trial of idursulfase, a recombinant enzyme replacement therapy for this disorder, demonstrated significant improvement in a 6-min walk test and in pulmonary function tests, and a decrease in liver and spleen size among those receiving active therapy once weekly. Major side effects include allergic reactions, which generally are easily managed and do not require discontinuing therapy. Idursulfase is now approved in the US, and should provide significant improvement in quality of life for these individuals. This article reviews the disease and treatment, with comments on future therapeutic directions.
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PMID:Idursulfase: enzyme replacement therapy for mucopolysaccharidosis Type II (Hunter syndrome). 3074 45

Mucopolysaccharidosis type II (MPS II) is one of the most common mucopolysaccharidoses, which is caused by mutation of the gene encoding iduronate 2-sulfatase (IDS). The loss of function of IDS leads to the accumulation of heparan sulfate and dermatan sulfate of glycosaminoglycans throughout the body, resulting in skeletal deformities, mental retardation, rigid joints, and thick skin. Recently, enzyme replacement therapy has become a common strategy for treating this condition. However, its effectiveness on the central nervous system (CNS) is limited because intravenously administered recombinant IDS (rIDS) cannot pass through the blood brain barrier. Therefore, several methods for delivering rIDS to the CNS, using anti-human transferrin receptor antibody and adeno-associated virus 9, have been explored. To investigate additional approaches for treatment, more cognition about the intracellular dynamics of mutant IDS is essential. We have already found that mutant IDS accumulated in the endoplasmic reticulum (ER) and was degraded by ER-associated degradation (ERAD). Although the dynamics of degradation of mutant IDS was revealed, the molecular mechanism related to the folding of mutant IDS in the ER remained unclear. In this research, we confirmed that mutant IDS retained in the ER would be folded by binding with calnexin (CNX). Thus, knockdown of CNX reduced the translocation of mutant IDS from ER to lysosome and its enzyme activity, indicating that the correct folding of this protein via interaction with CNX ensures its functional activity. These findings reveal the possibility that modifying the interaction of mutant IDS and CNX could contribute to alternative therapeutic strategies for MPS II.
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PMID:Calnexin promotes the folding of mutant iduronate 2-sulfatase related to mucopolysaccharidosis type II. 3102 29


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