Defects in lysosomal enzyme protection: galactosialidosis

Oligosaccharidoses

10.1093/med/9780199972135.003.0057 ◽

2016 ◽

Author(s):

Antonio Federico ◽

Silvia Palmeri

Keyword(s):

Supportive Care ◽

Lysosomal Enzyme ◽

Lysosomal Storage Disorders ◽

Clinical Spectrum ◽

Lysosomal Storage ◽

Primary Defect ◽

Lysosomal Diseases ◽

Enzyme Protection ◽

Schindler Disease ◽

Storage Disorders

Oligosaccharidoses are a group of lysosomal diseases, also called glycoproteinoses, biochemically characterized by storage of protein-bound oligosaccharides within lysosomes and excretion with urine of corresponding sugars. Storage of oligosaccharides results from absence or defective function of a specific lysosomal enzyme. Classification includes α‎ and β‎ mannosidosis, fucosidosis, sialidosis types I and II, Schindler disease, and aspartylglycosaminuria. Galactosialidosis characterized by deficiency of β‎-galactosidase and α‎-neuraminidase with presence in patient urine of oligosaccharides has been included among oligosaccharidoses but may be better classified as a lysosomal enzyme protection defect disease in relation to its primary defect of cathepsine A-protective protein. The clinical spectrum of the diseases vary widely, as is common in lysosomal storage disorders. Patients frequently have neurological symptoms, but in rare cases presenting in adulthood symptoms may be very subtle. Psychiatric presentations have been described in adults. For adult cases, no treatments are available except for supportive care.

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Ultrastructure of Fibroblast Cultures, Lymphocytes, and Liver in Mucopolysaccharidoses Types I, II, III, IV, and VI.

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100068011 ◽

1970 ◽

Vol 28 ◽

pp. 204-205

Author(s):

George Hug ◽

William K. Schubert ◽

Shirley Soukup

Keyword(s):

Lysosomal Enzyme ◽

Apparent Lack ◽

Fibroblast Cultures ◽

Lysosomal Diseases ◽

Disease Specificity ◽

Deficient Activity

McKusick subdivided the syndrome of mucopolysaccharidoses into six types according to clinical, roentenographic, and genetic criteria and to the kind of mucopolysaccharide(s) excreted in the urine (1). Deficient activity of a lysosomal enzyme, (β-galactosidase, has recently been reported in types I, II and III of mucopolysaccharidoses as well as in generalized gangliosidosis (2). This apparent lack of disease specificity makes the enzymatic deficiency difficult to interpret. Nevertheless, the involvement of a lysosomal enzyme tends to characterize these disorders as lysosomal diseases.

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Electron Microscopy in the diagnosis of lysosomal storage diseases

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100156316 ◽

1989 ◽

Vol 47 ◽

pp. 866-867

Author(s):

Carole Vogler ◽

Harvey S. Rosenberg

Keyword(s):

Electron Microscopy ◽

Lysosomal Enzyme ◽

Rectal Mucosa ◽

Lysosomal Storage Diseases ◽

Cell Types ◽

Lysosomal Storage ◽

Storage Material ◽

Ultrastructural Examination ◽

Blood Leukocytes ◽

Storage Diseases

Diagnostic procedures for evaluation of patients with lysosomal storage diseases (LSD) seek to identify a deficiency of a responsible lysosomal enzyme or accumulation of a substance that requires the missing enzyme for degradation. Most patients with LSD have progressive neurological degeneration and may have a variety of musculoskeletal and visceral abnormalities. In the LSD, the abnormally diminished lysosomal enzyme results in accumulation of unmetabolized catabolites in distended lysosomes. Because of the subcellular morphology and size of lysosomes, electron microscopy is an ideal tool to study tissue from patients with suspected LSD. In patients with LSD all cells lack the specific lysosomal enzyme but the distribution of storage material is dependent on the extent of catabolism of the substrate in each cell type under normal circumstances. Lysosmal storages diseases affect many cell types and tissues. Storage material though does not accumulate in all tissues and cell types and may be different biochemically and morphologically in different tissues.Conjunctiva, skin, rectal mucosa and peripheral blood leukocytes may show ultrastructural evidence of lysosomal storage even in the absence of clinical findings and thus any of these tissues can be used for ultrastructural examination in the diagnostic evaluation of patients with suspected LSD. Biopsy of skin and conjunctiva are easily obtained and provide multiple cell types including endothelium, epithelium, fibroblasts and nerves for ultrastructural study. Fibroblasts from skin and conjunctiva can also be utilized for the initiation of tissue cultures for chemical assays. Brain biopsy has been largely replaced by biopsy of more readily obtained tissue and by biochemical assays. Such assays though may give equivical or nondiagnostic results and in some lysosomal storage diseases an enzyme defect has not yet been identified and diagnoses can be made only by ultrastructural examination.

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Effect of Calcium ion on the interaction between Thrombin and Heparin. Thermal Denaturation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651883 ◽

1977 ◽

Vol 38 (03) ◽

pp. 0677-0684 ◽

Cited By ~ 6

Author(s):

Raymund Machovich ◽

Péter Arányi

Keyword(s):

Calcium Ions ◽

Rate Constants ◽

Thermal Denaturation ◽

Time Course ◽

Complex Analysis ◽

Heat Inactivation ◽

Second Phase ◽

Denaturation Kinetics ◽

Enzyme Protection ◽

Enzyme Denaturation

SummaryHeat inactivation of thrombin at 54° C followed first order kinetics with a rate constant of 1.0 min−1 approximately. Addition of heparin resulted in protection against thermal denaturation and, at the same time, rendered denaturation kinetics more complex. Analysis of the biphasic curve of heat inactivation in the presence of heparin revealed that the rate constants of the second phase changed systematically with heparin concentrations. Namely, at 4.5 × 10−6M, 9 × 10−6M, 1.8 × 10−5M and 3.6 × 10−5M heparin concentrations, the rate constants were 0.27 min−1, 0.17 min−1, 0.11 min−1 and 0.06 min−1, respectively.Sulfate as well as phosphate ions displayed also enzyme protection against heat inactivation, however, the same effect was obtained already at a heparin concentration, lower by three orders of magnitude.The kinetics of enzyme denaturation was not affected by calcium ions, whereas in the presence of heparin the inactivation rate of thrombin changed, i. e. calcium ions abolished the biphasic character of time course of thermal denaturation.Thus, the data suggest that calcium ions contribute to the effect of heparin on thrombin.

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