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At least 19 recordsLinked to original sources
PubMed1976

Angiokeratoma corporis diffusum (Fabry disease). A lysosomal disease.

Angiokeratoma corporis diffusum (Fabry disease) is an X-linked recessive disease. We had an opportunity to examine a heterozygous female patient with angiokeratoma and cornea verticillata. The patient's serum alpha-galactosidase activity was reported to be about 50% of normal. Skin lesion biopsy specimens were stained with electron microscopic acid phsophatase (ACP), with proper controls. Acid phosphatase activity was demonstrable within membrane-bound inclusions of cutaneous vascular endothelial cells. This suggested that the accumulation of abnormal glycolipids in the vascular cells occurs in the lysosomes.

Acid Phosphatase↗
PubMed1978

Sialogluciduria in lysosomal diseases: quantitative and qualitative analysis of urinary low molecular sialoglucides from patients with mucopolysaccharidosis and with mucolipidosis.

Low molecular sialoglucides were isolated from the urines of normal human male and two patients with lysosomal disease (mucopolysaccharidosis type II and a new type of mucolipidosis) by charcoal adsorption method. Urinary sialoglucides were fractionated into two fractions (SG-1 and SG-2) by Sephadex G-25 gel filtration and considerable increase in excretion of SG-1 was observed in the patients with lysosomal diseases: two- to three-fold increase in mucopolysaccharidosis type II and seven- to eight-fold increase in mucolipidosis. SG-1 was further fractionated into 18 to 19 fractions by Sephadex G-50 gel filtration and ion exchange chromatography. Comparison of the amounts and the chemical compositions of these fractions suggested that the increase in SG-1 was dependent upon the increase in excretion of low molecular sialoglucides rich in mannose and N-acetylglucosamine.

Amino Acids↗
PubMed1978

Lysosomal acid hydrolases in established lymphoblastoid cell lines, transformed by Epstein-Barr virus, from patients with genetic lysosomal storage diseases.

Lysosomal acid hydrolases were determined in established lymphoblastoid cell lines, transformed in vitro by Epstein-Barr virus (EBV) from lymphocyte-rich cell populations isolated from the peripheral blood of patients with genetic lysosomal storage diseases--Hurler syndrome, Scheie syndrome, GM1-gangliosidosis type 1 and type 2, Tay-Sachs disease, and I-cell disease--and from obligate heterozygotes for these diseases. The respective enzyme activity was undectectable in lymphoblastoid cells from the patients, but not from controls. Obligate heterozygotes could not always be distinguished from controls in lymphoblastoid cells as well as in leukocytes. These results suggest that established lymphoblastoid cell lines are useful material for the enzymatic study of genetic lysosomal storage diseases.

Cell Line↗
PubMed2026

Biologic Therapies for Alleviating Neurodegeneration in Lysosomal Storage Diseases.

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders characterized by lysosomal dysfunction and progressive accumulation of undegraded substrates, leading to multisystem involvement and, in many cases, severe neurodegeneration. Because the blood-brain barrier (BBB) restricts central nervous system (CNS) access for most therapeutic modalities, neurological manifestations remain the major unmet need across LSDs. In this review, we summarize current and emerging strategies aimed at correcting CNS pathology, including enzyme replacement therapy (ERT), adeno-associated virus (AAV)-mediated gene therapy, allogeneic hematopoietic stem cell transplantation (HSCT), and autologous HSCT with gene-modified hematopoietic stem cells. While ERT provides limited CNS benefits and allogeneic HSCT mitigates neurodegeneration only partially, their overall impact on CNS outcomes remains restricted. Newer approaches, such as BBB-shuttling ERTs, CNS-tropic AAV capsids, and genetically modified autologous hematopoietic stem and progenitor cells capable of sustained supraphysiological enzyme production, offer promising avenues for enhanced CNS delivery and cross-correction. Together, these advances underscore a shift toward integrated therapeutic strategies that combine systemic and CNS-directed interventions, with the potential to transform outcomes for patients with LSDs and other neurodegenerative disorders amenable to cross-correction.

Journal Article↗
PubMed1978

Computerized axial tomography and cerebral scintigraphy in leukodystrophy. A study of two boys presumably suffering from lysosomal disease.

Two unrelated boys, 12 and 9 years old, suffered from a diffuse cerebral disease that followed a parallel, subacute course. Mental regression, loss of hearing and vision, spastic-ataxic and pseudobulbar disturbances, and atrophy of the optic nerves occurred in both. Enzyme studies and the liver biopsy of one of the patients suggest a "lysosomal disease." The hallmark of both patients is the striking similarity of the cerebral scintigraphy and the computerized axial tomography (CT). Cerebral scintigraphy showed annular and crescent-shaped areas of increased radioactivity in the parietoccipital region. The CT indicated bilateral, symmetric bands of elevated density after contrast enhancement in the paraventricular white matter in the same region. These findings and the neurologic symptoms are compatible with leukodystrophy. Thus cerebral scintigraphy and CT appear to be useful aids in the diagnosis of metabolic brain disease. Computerized axial tomography is preferred for distinguishing whether lesions are in white or gray matter.

Brain↗
PubMed1977

Lysosomal enzymes in medium from cultured skin fibroblasts from normal individuals and patients with lysosomal diseases.

The release of acid hydrolases from cultured skin fibroblasts into the cell culture medium was studied in several lysosomal storage disorders (GM1-gangliosidosis, Fabry's disease, Hurler's disease, mannosidosis, and mucolipidosis). The levels of different activities were proportional to time (up to 44 h after medium change) and cell density with the exception of beta-glucosidase, which was not released. Culture medium from the fibroblasts of mucolipidosis patients exhibited higher activity of acid hydrolases than medium from cells of patients with GM1-gangliosidosis, Fabry's disease, Hurler's disease, and mannosidosis. These cells, however, exhibited somewhat higher levels of enzyme activity in their culture medium than control fibroblasts. The total production of acid hydrolases was yet rather similar in fibroblasts from controls and patients. Differential centrifugation showed that the highest specific activity of acid hydrolases was seen, as expected, in the lysosomal fraction, except in fibroblasts from patients with mucolipidosis, where the supernatant exhibited most activity. beta-Glucosidase, however, showed a normal differential centrifugation pattern also in fibroblasts from these patients.

Carbohydrate Metabolism, Inborn Errors↗
PubMedDate not supplied

[Enzyme diagnostics in lysosomal diseases with emphasis on sphingolipidoses].

The authors describe the conditions and results of the enzymatic diagnosis in various sphingolipidoses, based on their personal experience. A precise diagnosis can be presently made on white blood cells, cultured fibroblasts or amniotic cells, and in some cases on serum or urine. In most cases the use of artificial substrates allows a relatively simple diagnosis. The methods are quantitative or qualitative (especially cellulose acetate electrophoresis, of which a few pictures are shown). The results are particularly clear in Tay-Sachs disease and its variants. Despite the fatal prognosis of most sphingolipidoses it is important to ensure a precise and precocious diagnosis. This is of prime value when a prenatal detection of the disease is considered in case of a future pregnancy.

Amniotic Fluid↗
PubMedDate not supplied

Lysosomal storage diseases.

The majority of lysosomal storage diseases affect the central nervous system. Those that reflect a primary lysosomal disorder are associated with genetically determined deficiencies of specific lysosomal enzymes and storage of the relevant substrate. Autofluorescent lipopigments accumulate in the ceroid-lipofuscinoses, a heterogeneous group of diseases in which lysosomal storage is thought to be a secondary event. In animals, there occurs a group of toxic storage diseases whose pathology mimics that of some of the genetic diseases. In humans some element of control may be achieved by heterozygote detection programmes and/or prenatal diagnosis of pregnancies at risk with elective abortion of an affected foetus. The outlook for specific therapy is not encouraging at this stage.

Enzymes↗
PubMed1978

[Pathobiochemical aspects of lysosomal enzymes with special reference to lysosomal storage diseases (author's transl)].

Lysosomal hydrolases participate substantially in the degradation of all classes of biological macromolecules. They act physiologically within the lysosome. The enzymes are either primarily included within primary lysosomes or are transported to these cell organelles after secretion and subsequent adsorptive pinocytosis. The involvement of these enzymes in a variety of pathological conditions can be understood on the basis of the known functions of lysosomal hydrolases. Inactivity of one or several of the enzymes causes lysosomal storage disorders. Similar metabolic consequences are found when the enzymes are unable to be concentrated within the lysosome. Lysosomal hydrolases participate, furthermore, in the pathogenesis of numerous diseases. A distinction can be made between lysosomal overload, pathologically-increased enzyme secretion into the extracellular space, and a release of lysosomal enzymes into the cytosol.

Acid Phosphatase↗
PubMed1979

[Hereditary lysosomal storage diseases (author's transl)].

The literature on hereditary lysosomal storage diseases occurring in man and various domestic animals is reviewed. These forms of disease are usually recessively autosomally heritable and are reflected in partial or total deficiency of a lysosomal enzyme, resulting in accumulation of metabolites. The majority of these lysosomal storage diseases show a predilection for localization in the nervous system. As a rule, the main clinical features are neurological symptoms. The first symptoms are usually observed at an early age and the disease is marked by the fact that it is familial in character. Heterozygotes may be identified by controlled haematological studies in a number of these diseases. In domestic animals, these forms of disease may serve as models for human pathology and some may be of economic importance, such as mannosidosis of Angus cattle in New Zealand and GM1 gangliosidosis of Friesian cattle in Ireland.

Animals↗
PubMed1992

Mutations causing aspartylglucosaminuria (AGU): a lysosomal accumulation disease.

This article provides a review of the mutations reported so far in the lysosomal storage disease aspartylglucosaminuria (AGU). The clinical symptoms, biochemical findings, and diagnostic possibilities of the disease are introduced. The prevalence and biological consequences of the found mutations are then described, as well as the availability of a new rapid DNA test suitable for carrier screening. This test will be especially applicable in the genetically isolated Finnish population, where the carrier frequency of AGU was found to be as high as 1:36. Finally, future prospects dealing with the foreseeable therapeutic interventions of the disease are discussed.

Acetylglucosamine↗
PubMed1979

Ultrastructure of skin biopsy specimens in lysosomal storage diseases: common sources of error in diagnosis.

Common sources of error in the diagnosis of lysosomal storage diseases by ultrastructural examination of skin specimens have been identified in a series of biopsies from 72 patients. Four principal factors have emerged as leading pitfalls and sources of error in diagnosis. First, the skin biopsy technique itself may lead to alterations of normal skin ultrastructure. Second, artifacts may be produced during fixation and preparation of tissue for electron microscopy. Third, cellular organelles and structures normally present in human skin may be mistakenly interpreted as pathological. Fourth, the use of cultured skin fibroblasts for ultrastructural identification of storage material is often accompanied by artifacts induced in tissue culture and is not recommended. Recognition of these common problems may aid interpretation of the fine structure of skin abnormalities. Furthermore, when skin biopsy specimens are used as the primary source of diagnostic material, correlation of both skin ultrastructure and assay for specific lysosomal enzymes in cultured dermal fibroblasts will facilitate diagnostic accuracy.

Biopsy↗
PubMed1977

A suspected lysosomal storage disease in Abyssinian cats. Part II: histopathological and ultrastructural aspects.

The histopathological and ultrastructural findings in the central nervous system and lymphoid tissue of Abyssinian kittens suffering from a disease which was clinically characterised by neurological disturbances, are described. The lesions were vacuolisation of neurones and macrophages with light microscopy and lamellated membranous cytoplasmic bodies, initially in lysosomes with electron microscopy. Irregularly shaped membrane-bound bodies with an amorphous substance were eventually formed in the cytoplasm of affected cells. It is considered that this is a lysosomal storage disease.

Animals↗
PubMed1978

The cherry red spot-myoclonus syndrome: a newly recognized inherited lysosomal storage disease due to acid neuraminidase deficiency.

A newly discovered lysosomal storage disorder, apparently transmitted as an autosomal recessive trait, presents with cherry red spots in childhood, progressive debilitating myoclonus, insidious visual loss, and normal intelligence. Somatic and bony abnormalities are not evident clinically. Neuronal lipidosis and vacuolated Kuppfer cells are found upon tissue examination. The diagnosis can be most easily confirmed by chromatographic screening for urinary sialyloligosaccharides. The primary enzyme defect is a deficiency of an acid neuraminidase isoenzyme which cleaves sialyloligosaccharides. I discuss here the clinical phenotype in four patients, the chemical abnormality, the pathogenesis, the enzyme defect and the molecular genetics of this disorder.

Adolescent↗
PubMed1979

Transport of radiolabelled glycoprotein to cell surface and lysosome-like bodies of absorptive cells in clutured small-intestinal tissue from normal subjects and patients with a lysosomal storage disease.

The transport of 3H-fucose- and 3H-glucosamine-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue was investigated with light- and electron-microscopical autoradiography. The findings showed that these glycoproteins were completed in the Golgi apparatus and transported in small vesicular structures to the apical cytoplasm of these cells. Since this material arrived in the cell coat on the microvilli and in the lysosome-like bodies simultaneously, a crinophagic function of these organelles in the regulation of the transport or secretion of cell-coat material was supported. In the absorptive cells of patients with fucosidosis or Hunter's type of lysosomal storage disease, a smiliar transport of cell-coat material to the lysosome-like bodies and a congenital defect of a lysosomal hydrolase normally involved in the degradation of cell-coat material, can explain the accumulation of this material in the dense bodies.

Adolescent↗