Disease relevance of Mucopolysaccharidosis I

• A defect of the lysosomal enzyme alpha-L-iduronidase (IDUA) interrupts heparan and dermatan sulfate degradation and causes neuropathology in children with severe forms of mucopolysaccharidosis type I (MPSI, Hurler syndrome) [1].
• The defects causing Huntington's disease, facioscapulohumeral muscular dystrophy, piebaldism, Hurler/Scheie syndrome, one form of autosomal recessive retinitis pigmentosa, and a second locus for autosomal dominant polycystic kidney disease have recently been localized to chromosome 4 [2].
• Several scores of patients with diseases as diverse as metachromatic leukodystrophy, adrenoleukodystrophy, globoid cell leukodystrophy, Hurler syndrome (MPS I-H), Maroteaux-Lamy (MPS VI) Gaucher disease, and fucosidosis have been successfully treated following long-term engraftment [3].
• The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy [4].
• Vital staining with the fluorescent dye, acridine orange, was evaluated as a means of detecting abnormalities of lysosomes in cultivated fibroblasts of patients with macular corneal dystrophy and mucopolysaccharidoses types I-H (Hurler's syndrome) and type II (Hunter's syndrome) [5].

Psychiatry related information on Mucopolysaccharidosis I

• Results suggests that BMT for Hurler syndrome, adrenoleukodystrophy, and globoid cell leukodystrophy can be effective in preventing dementia if done early enough in the disease [6].

High impact information on Mucopolysaccharidosis I

• Termination of pregnancy was performed in 3 patients on the basis of cytogenetic abnormalities (47,XXY, 47,XXX, 47,XY 21+): in 2 patients with anencephalic fetuses on the basis of alpha-fetoprotein and ultrasound investigations, and 1 patient with fetal Hurler's syndrome [7].
• Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area [8].
• Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation [9].
• We describe here the generation of a murine model for Hurler syndrome by targeted disruption of the murine Idua gene [10].
• Unstimulated human lung fibroblasts (HFL-1) secreted TIMP at the rate of approximately 2 micrograms/10(6) cells/24 h, and normal foreskin fibroblasts (HS 27) and skin fibroblasts from a patient with Hurler's disease (GM 1391) secreted TIMP at 0.3 and 0.2 micrograms/10(6) cells/24 h, respectively [11].

Chemical compound and disease context of Mucopolysaccharidosis I

• Mutual correction of co-cultivated fibroblasts from patients with Hunter's and Hurler's syndrome could be inhibited by either fructose 1-phosphate or mannose 6-phosphate [12].
• Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation [13].
• Excellent discrimination between normal and affected pregnancies was provided by an estimation of the dermatan sulphate:chondroitin sulphate ratio (Hurler disease) and the heparan sulphate: chondroitin sulphate ratio (Sanfilippo disease); the use of external glycosaminoglycan standards was then unnecessary [14].
• Comparison of the substrate 4-methylumbelliferyl-alpha-l-iduronide with phenyl-alpha-L-iduronide for the diagnosis of Hurler's disease in cultured cells [15].
• Fludarabine-based protocol for haploidentical peripheral blood stem cell transplantation in Hurler syndrome [16].

Anatomical context of Mucopolysaccharidosis I

• Bone marrow transplantation has provided a method for treatment of adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome [17].

Gene context of Mucopolysaccharidosis I

• Hurler syndrome with cardiomyopathy in infancy [18].
• The findings of a markedly attenuated Bowman's layer and FLS collagen may be abnormalities specific to Scheie's syndrome resulting from the altered glycosaminoglycan composition of the extracellular matrix [19].
• Two had MPS I S, one had MPS IIA, two had MPS IIB, two had MPS IIIB, and one had MPS VI [20].
• We describe the initial experience with combined use of enzyme replacement therapy (ERT, laronidase) and HSCT in Hurler syndrome [21].
• Histochemical study of Hurler's disease by the use of peroxidase-labelled lectins [22].

Analytical, diagnostic and therapeutic context of Mucopolysaccharidosis I

• Use of 4-trifluoromethylumbelliferyl-alpha-L-iduronide as a new substrate for detection of alpha-L-iduronidase deficiency in human tissues and for rapid prenatal diagnosis of Hurler disease [23].
• Heparan sulfate and dermatan sulfate from the liver of a patient with Hurler syndrome: high performance liquid chromatography of their degradation products after incubation with alpha-L-iduronidase-deficient fibroblasts [24].

References