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)

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

Mucopolysaccharidosis (MPS) is a rare metabolic disease characterized by abnormal accumulation and excretion of mucopolysaccharides. Patients with MPS have many anesthetic problems including ischemic heart disease, valve insufficiency, difficult intubation, joint stiffness and mental retardation. We report a case of Scheie syndrome, a mild type of MPS, which presented a unique problem of difficult intubation. The patient was a 35 year old woman, scheduled for anterior fixation of the 4th lumbar vertebra. Her manifestations included low height, corneal clouding and systemic joint stiffness. Coronary artery disease was suspected from ECG. There was no mental retardation. Mouth opening was possible for about 4.5 cm. After induction with fentanyl, thiopental and vecuronium, intubation under laryngoscopy was tried but impossible because mouth opening was restricted to only 2 cm. Therefore muscle relaxant was reversed with neostigmine and atropine. Then under spontaneous respiration, she was intubated using a bronchofiberscope. It is difficult to explain why her mouth opening was more restricted after induction. We suspect mechanical change of temporomandibular joint or low compliance of the muscles. In conclusion, as reported previously, spontaneous respiration should be maintained until intubation. Especially in a patient with Scheie syndrome, whose mental development is normal, fiberoptic intubation should prove to be useful.
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PMID:[Anesthesia in a patient with Scheie syndrome]. 796 40

Mucopolysaccharidosis type I (i.e., Hurler, Hurler-Scheie, and Scheie syndromes) and type II (i.e., Hunter syndrome) are lysosomal storage disorders resulting from alpha-L-iduronidase (IDUA) deficiency and iduronate-2-sulfatase (IDS) deficiency, respectively. The a priori probability that both disorders would occur in a single individual is approximately 1 in 5 billion. Nevertheless, such a proband was referred for whom clinical findings (i.e., a male with characteristic facies, dysostosis multiplex, and mental retardation) and biochemical tests indicated these concomitant diagnoses. In repeated studies, leukocyte 4 methylumbelliferyl-alpha-L-iduronidase activities in this kindred were as follows: <1.0 nmol/mg protein/h in the proband and proband's clinically normal sister; 45.3 in mother; and 45.7 in father (normal range 65.0-140). Leukocyte L-O-(alpha-iduronate-2-sulfate)-(1->4)-D-O-2,5-anhydro[1-3H]mannitol-6- sulfate activities were as follows: 0.0 U/mg protein/h in the proband; 5.7 in his sister; 4.9 in mother; and 15.0 in father (normal range 11.0-18.4). Multiple techniques, including automated sequencing of the entire IDS and IDUA coding regions, were employed to unravel the molecular genetic basis of these intriguing observations. The common IDS mutation R468W was identified in the proband, his mother, and his sister, thus explaining their biochemical phenotypes. Additionally, the proband, his sister, and his father were found to be heterozygous for a common IDUA mutation, W402X. Notably, a new IDUA mutation A300T was also identified in the proband, his sister, and his mother, accounting for reduced IDUA activity in these individuals; the asymptomatic sister, whose cells demonstrated normal glycosaminoglycan metabolism, is thus a compound heterozygote for W402X and the new allele. This A300T mutation is the first IDUA pseudodeficiency gene to be elucidated at the molecular level.
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PMID:Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency. 855 71

The lysosomal storage disorder, mucopolysaccharidosis type I (MPS I), is caused by a deficiency of the enzyme alpha-L-iduronidase, which is involved in the breakdown of dermatan and heparan sulphates. There are three clinical phenotypes, ranging from the Hurler form characterised by skeletal abnormalities, hepatosplenomegaly and severe mental retardation, to the milder Scheie phenotype where there is aortic valve disease, corneal clouding, limited skeletal problems, but no mental retardation. In this study, 85 MPS I families (73 Hurler, 5 Hurler/Scheie, 7 Scheie) were screened for 9 known mutations (Q70X, A75T, 474-2a>g, L218P, A327P, W402X, P533R, R89Q, 678-7g>a). W402X was the most frequent mutation in our population (45.3%) and Q70X was the second most frequent (15.9%). In 30 families, either one or both of the mutations were not identified, which accounted for 25.9% of the total alleles. Therefore, all 14 exons of the alpha-L-iduronidase gene were screened in these patients and 23 different sequence changes were found, 17 of which were previously unknown. The novel sequence changes include 4 deletions (153delC, 628del5, 740delC, 747delG), 5 nonsense mutations (Q60X, Y167X, Q400X, R619X, R628X), 6 missense mutations (C205Y, G208V, H240R, A319V, P496R, S633L), a splice site mutation (IVS12+5g>a), and a rare polymorphism (A591T). The polymorphism and novel missense mutations were transiently expressed in COS-7 cells and all of them except the polymorphism showed complete loss of enzyme activity. In total, 165 of the 170 mutant alleles were identified in this study and despite the high frequency of W402X and Q70X, the identification of many novel mutations unique to individual families further highlights the genetic heterogeneity of MPS I.
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PMID:Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. 1173 25

Mucopolysaccharidosis I (MPS I) is a rare, recessively inherited, lysosomal storage disorder caused by deficiency on the enzyme a-L-iduronidase. This defect results in accumulation of heparan and dermatan sulfate in different tissues and organs due to a deficiency in the catabolism of glycosaminoglycans. The overall incidence of MPS I is 0.99-1.99/100.000 live births. There are three clinical presentations: Hurler (severe), Hurler Scheie (mild) and Scheie (mild). We report the case of a 10-years-old male patient diagnosed with Hurler syndrome, the severe presentation, 5 years ago by enzyme a-L-iduronidase activity measurement in leukocytes; with a history of recurrent respiratory infections, umbilical hernia, corneal opacity, coarse facial features, macroglossia, hearing loss, stiffness of joints, cardiac compromise, claw hands, mental retardation and stunted growth. After enzyme replacement therapy the patient has shown improvement of visceral symptoms, but the neurological damage continuous in progress.
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PMID:[Mucopolysaccharidosis I, Hurler syndrome: a case report]. 2307 Jan 90

The mucopolysaccharidoses are a heterogeneous group of inherited lysosomal storage disorders, characterized by the accumulation of undegraded glycosaminoglycans in various organs, leading to tissue damage. Mucopolysaccharidoses include eight individual disorders (IS [Scheie syndrome], IH [Hurler syndrome], II, III, IV, VI, VII and IX). They have autosomal-recessive transmission with the exception of mucopolysaccharidosis II, which is X-linked. Each individual disorder has a wide spectrum of phenotypic variation, depending on the specific mutation, from very mild to very severe. The skeletal and central nervous systems are particularly affected. The typical clinical presentation includes organomegaly, dysostosis multiplex with short trunk dwarfism, mental retardation and developmental delay. In this article, we review the neuroimaging manifestations of the different types of mucopolysaccharidoses including the dysostosis multiplex of the skull and spine as well as the various central nervous system complications. These include white matter injury, enlargement of the perivascular spaces, hydrocephalus, brain atrophy, characteristic enlargement of the subarachnoid spaces as well as compressive myelopathy. The correlation between several of the neuroimaging features and disease severity remains controversial, without well-established imaging biomarkers at this time. Imaging has, however, a crucial role in monitoring disease progression, in particular craniocervical junction stenosis, cord compression and hydrocephalus, because this allows for timely intervention before permanent damage occurs.
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PMID:Mucopolysaccharidoses: overview of neuroimaging manifestations. 2975 20