Fluorophore-assisted electrophoresis of urinary carbohydrates for the identification of patients with oligosaccharidosis-and mucopolysaccharidosis-type lysosomal storage diseases

1994 ◽  
Vol 1 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Christopher M. Starr ◽  
John C. Klock ◽  
Elisa Skop ◽  
Irene Masada ◽  
Tullio Giudici
Keyword(s):  
Lysosomal Storage Diseases ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Storage Diseases

Behavior and Therapeutic Efficacy of β-Glucuronidase–Positive Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type VII

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2142-2150 ◽  
Author(s):  
Brian J. Freeman ◽  
Marie S. Roberts ◽  
Carole A. Vogler ◽  
Andrew Nicholes ◽  
A. Alex Hofling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Therapeutic Efficacy ◽  
Lysosomal Storage Diseases ◽  
Reticuloendothelial System ◽  
Mononuclear Phagocytes ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Mps Vii

Abstract Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted β-glucuronidase–positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MPS VII). Cell surface marking studies indicate that the bone marrow-derived cells are less mature than the peritoneal macrophages. However, both cell types retain the ability to home to tissues rich in cells of the reticuloendothelial system after intravenous injection into MPS VII mice. The half-life of both types of donor macrophages is approximately 7 days, and some cells persist for at least 30 days. In several tissues, therapeutic levels of β-glucuronidase are present, and histopathologic analysis demonstrates that lysosomal storage is dramatically reduced in the liver and spleen. Macrophages intravenously injected into newborn MPS VII mice localize to the same tissues as adult mice but are also observed in the meninges and parenchyma of the brain. These data suggest that macrophages play a significant role in the therapeutic efficacy of BMT for lysosomal storage diseases and may have implications for treatments such as gene therapy.

scholarly journals Implementation of Second-Tier Tests in Newborn Screening for Lysosomal Disorders in North Eastern Italy

2019 ◽  
Vol 5 (2) ◽  
pp. 24 ◽  
Author(s):  
Alberto B. Burlina ◽  
Giulia Polo ◽  
Laura Rubert ◽  
Daniela Gueraldi ◽  
Chiara Cazzorla ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Lysosomal Storage Diseases ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Lysosomal Disorders ◽  
North Eastern ◽  
Second Tier

The increasing availability of treatments and the importance of early intervention have stimulated interest in newborn screening for lysosomal storage diseases. Since 2015, 112,446 newborns in North Eastern Italy have been screened for four lysosomal disorders—mucopolysaccharidosis type I and Pompe, Fabry and Gaucher diseases—using a multiplexed tandem mass spectrometry (MS/MS) assay system. We recalled 138 neonates (0.12%) for collection of a second dried blood spot. Low activity was confirmed in 62 (0.06%), who underwent confirmatory testing. Twenty-five neonates (0.02%) were true positive: eight with Pompe disease; seven with Gaucher disease; eight with Fabry disease; and two with Mucopolysaccharidosis type I. The combined incidence of the four disorders was 1 in 4497 births. Except for Pompe disease, a second-tier test was implemented. We conclude that newborn screening for multiple lysosomal storage diseases combined with a second-tier test can largely eliminate false-positives and achieve rapid diagnosis.

Behavior and Therapeutic Efficacy of β-Glucuronidase–Positive Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type VII

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2142-2150 ◽  
Author(s):  
Brian J. Freeman ◽  
Marie S. Roberts ◽  
Carole A. Vogler ◽  
Andrew Nicholes ◽  
A. Alex Hofling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Therapeutic Efficacy ◽  
Lysosomal Storage Diseases ◽  
Reticuloendothelial System ◽  
Mononuclear Phagocytes ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Mps Vii

Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted β-glucuronidase–positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MPS VII). Cell surface marking studies indicate that the bone marrow-derived cells are less mature than the peritoneal macrophages. However, both cell types retain the ability to home to tissues rich in cells of the reticuloendothelial system after intravenous injection into MPS VII mice. The half-life of both types of donor macrophages is approximately 7 days, and some cells persist for at least 30 days. In several tissues, therapeutic levels of β-glucuronidase are present, and histopathologic analysis demonstrates that lysosomal storage is dramatically reduced in the liver and spleen. Macrophages intravenously injected into newborn MPS VII mice localize to the same tissues as adult mice but are also observed in the meninges and parenchyma of the brain. These data suggest that macrophages play a significant role in the therapeutic efficacy of BMT for lysosomal storage diseases and may have implications for treatments such as gene therapy.

Electron Microscopy in the diagnosis of lysosomal storage diseases

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.

scholarly journals Sphingolipid lysosomal storage diseases: from bench to bedside

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Muna Abed Rabbo ◽  
Yara Khodour ◽  
Laurie S. Kaguni ◽  
Johnny Stiban
Keyword(s):  
Basic Research ◽  
Lysosomal Storage Diseases ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Late Nineteenth Century ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
The Past ◽  
Health And Disease ◽  
General Aspects

AbstractJohann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.

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