Sphingolipidoses (Sphingolipidosis)

A group of inherited metabolic disorders characterized by the intralysosomal accumulation of SPHINGOLIPIDS primarily in the CENTRAL NERVOUS SYSTEM and to a variable degree in the visceral organs. They are classified by the enzyme defect in the degradation pathway and the substrate accumulation (or storage). Clinical features vary in subtypes but neurodegeneration is a common sign.

Also Known As:

Networked: 241 relevant articles (2 outcomes, 21 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Glycogen Storage Disease Type II (Pompe's Disease)
2.	Mucopolysaccharidoses
3.	Mucolipidoses (Sialidosis)
4.	Type C Niemann-Pick Disease (Niemann Pick Disease, Type C)
5.	Neuronal Ceroid-Lipofuscinoses (Neuronal Ceroid Lipofuscinosis)

Experts

1.	Sandhoff, Konrad: 12 articles (12/2019 - 05/2003)
2.	Futerman, Anthony H: 6 articles (06/2015 - 08/2002)
3.	Kolter, Thomas: 6 articles (11/2011 - 05/2003)
4.	Ohno, Kousaku: 5 articles (04/2013 - 08/2004)
5.	Suzuki, Yoshiyuki: 5 articles (04/2013 - 08/2004)
6.	Ikonen, Elina: 4 articles (10/2019 - 02/2003)
7.	Bongarzone, Ernesto R: 4 articles (01/2019 - 11/2016)
8.	Ninomiya, Haruaki: 4 articles (11/2010 - 08/2004)
9.	Ogawa, Seiichiro: 4 articles (11/2010 - 08/2004)
10.	Pagano, Richard E: 4 articles (01/2005 - 11/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Sphingolipidoses:

1.	EnzymesIBA 10/20/1983 - "This is the first evidence of long-term in vivo enzyme replacement, accompanied by improved pathology, in a genetic sphingolipidosis." 07/01/1994 - "A study on enzyme activities of some sphingolipidoses." 11/01/1976 - "It is suggested that it should be of considerable value in those areas which require the rapid analysis of large numbers of samples, such as in screening for the sphingolipidoses or for enzyme purification studies." 10/01/1970 - "Further developments in studies in sphingolipidoses: "missing enzymes"." 01/01/1961 - "Studies on enzyme alterations in the infantile sphingolipidoses. "
2.	CholesterolIBA 09/01/2008 - "Their suggested functions include protection against oxidative stress, participation in signal transduction, membrane fusion events, cholesterol transport and membrane trafficking, processes known to be disturbed in sphingolipidoses. " 10/01/2019 - "HSP70 represents a major stress-inducible family member and has been identified as a druggable target in inherited cholesterol-sphingolipid storage diseases. " 01/01/2007 - "Rab8-dependent recycling promotes endosomal cholesterol removal in normal and sphingolipidosis cells." 11/03/2004 - "Interestingly, cells from patients suffering from sphingolipid storage diseases show high intracellular amounts of free cholesterol. " 02/01/2003 - "Niemann-Pick type C (NPC) disease is a fatal recessively inherited lysosomal cholesterol-sphingolipidosis. "
3.	SphingolipidsIBA 01/01/2016 - "Here we summarize MS and tandem MS methods used for qualitative and quantitative analysis of sphingolipids (SL) relative to the diagnostic process for sphingolipidoses and studies focusing on alterations in cell functions due to these disorders. " 01/01/2013 - "The relationship of sphingolipids with human disease first arose from the study of sphingolipid storage diseases over 50 years ago. " 11/01/2011 - "This method can be applied to investigate impairments of neutral sphingolipid metabolism in a variety of disorders such as sphingolipidoses and be employed to screen for sphingolipid profile changes as induced by knockout experiments or related studies." 10/31/2023 - "A sub group of these disorders are the sphingolipidoses in which sphingolipids accumulate in the lysosome. " 01/01/2021 - "We also identify parallels between the sphingolipidoses and more common forms of neurodegeneration, which both exhibit evidence of defective sphingolipid clearance in the nervous system."
4.	LipidsIBA 05/01/2003 - "Our work will be reviewed in light of studies from other laboratories, with particular emphasis on the use of models of sphingolipid storage diseases to determine how these lipids affect neuronal function." 10/05/2022 - "While this lysosphingolipid may behave like a protumorigenic agent, further investigations in appropriate models are needed to elucidate the role of these peculiar lipids, not only in sphingolipidoses but also in malignant diseases in general." 02/21/2020 - "In sphingolipidosis, lysosomal lipid storage occurs in both the central nervous system and visceral tissues, and central nervous system pathology is a common hallmark for all of them. " 01/01/2019 - "This mechanism serves also as a mechanistic model to understand how alterations of the membrane architecture by the progressive accumulation of lipids undermines cell function, with potential implications in other genetic sphingolipidoses and adult neurodegenerative conditions. " 11/01/2016 - "In this essay, we discuss a working hypothesis that brain cells in sphingolipidoses clear some of the accumulated lipid material to attempt restoring cell homeostasis via EV secretion. "
5.	GlycosphingolipidsIBA 01/01/2019 - "Sphingolipidoses are severe, mostly infantile lysosomal storage disorders (LSDs) caused by defective glycosphingolipid degradation. " 05/29/2003 - "A historical perspective of the glycosphingolipids and sphingolipidoses." 05/29/2003 - "Endocytic trafficking of glycosphingolipids in sphingolipid storage diseases." 12/01/2002 - "Endocytosis and sorting of glycosphingolipids in sphingolipid storage disease." 11/01/2002 - "Glycosphingolipids are endocytosed and targeted to the Golgi apparatus, but are mistargeted to lysosomes in numerous sphingolipidoses. "
6.	HydrolasesIBA 12/01/2010 - "As is the case for LSDs in general, most sphingolipidoses are caused by deficiencies in lysosomal hydrolases. " 03/12/1979 - "Sphingolipidoses are caused by recessively inherited deficiencies of lysosomal hydrolases. " 04/01/1978 - "[Clinical, preclinical and prenatal diagnosis of congenital sphingolipidoses by determining lysosomal hydrolases (author's transl)]." 12/01/2013 - "Inherited defects of hydrolases or SAPs or uptake of cationic amphiphilic drugs cause lipid accumulation, eventually leading to death, especially in inherited sphingolipid storage diseases. " 01/01/2013 - "The genetics of sphingolipid hydrolases and sphingolipid storage diseases."
7.	Proteins (Proteins, Gene)FDA Link 01/01/2023 - "Using two cell-based models of demyelinating sphingolipidoses, we demonstrate that altered lipid metabolism changes the abundance of specific plasma membrane proteins. " 12/01/2004 - "In 1984, the first activator protein was found and it expanded the concept of sphingolipidoses. " 01/01/1983 - "[Activator protein for the enzymic hydrolysis of sphingolipids and their relationships to sphingolipidosis. " 08/01/2014 - "Sphingolipidoses are inherited genetic diseases due to mutations in genes encoding proteins involved in the lysosomal catabolism of sphingolipids. " 03/01/2022 - "Here, lysosphingolipid and protein biomarkers of sphingolipidosis and neuropathology respectively, were assessed in plasma samples from 33 GM2 gangliosidosis patients, 13 GM1 gangliosidosis patients, and compared to 66 controls. "
8.	CeroidIBA 09/01/1976 - "Ultrastructural study of the skin biopsies of 23 patients with either ceroid-lipofuscinoses, mucopolysaccharidoses, mucolipidoses, acid maltase deficiency or sphingolipidoses, demonstrates the presence of relatively typical cytosomes allowing a precise diagnosis at least as early as the time of the first clinical evaluation." 03/01/1980 - "Skin and muscle biopsies were performed in 18 patients affected by various inborn storage disorders: mucopolysaccharidosis (MPS), sphingolipidosis, GM1 gangliosidosis, I-cell disease, ceroid-lipofuscinosis (CLF), adrenoleucodystrophy (ALD) and glycogenosis. " 01/01/1986 - "Genetic storage diseases with prominent myoclonus include classic infantile Tay-Sachs disease and juvenile neuropathic Gaucher's disease among the sphingolipidoses, most of the variants of the sialidoses and ceroid-lipofuscinoses, and Lafora disease. " 01/01/1980 - "We have studied the sphingolipidosis, principally, ceroid-lipofuscinosis and other complex lipid storage diseases. " 04/01/2013 - "Most frequent in this group are mtDNA mutations, inherited peripheral neuropathies, Charcot-Marie-Tooth disorders (CMT2A2, CMTX5), hereditary sensory neuropathy type 3 (HSAN3), Friedreich's ataxia, leukodystrophies, sphingolipidoses, ceroid-lipofuscinoses and neurodegeneration with brain iron accumulation. "
9.	Membrane LipidsIBA 11/01/2000 - "In this review, we summarize our studies of membrane lipid transport in sphingolipid storage disease (SLSD) fibroblasts. " 11/01/2016 - "Fluid levity of the cell: Role of membrane lipid architecture in genetic sphingolipidoses." 07/01/2007 - "An unglycosylated Sap-B variant, Asn215His, which causes a fatal sphingolipid storage disease, lost the ability to extract membrane lipids at acidic pH in the presence of BMP." 11/01/2016 - "Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism."
10.	Fatty Acids (Saturated Fatty Acids)IBA 08/01/2001 - "Lysosphingolipids, which lack the fatty acid moiety of sphingolipids, are known to be accumulated in some variants of sphingolipid storage diseases. " 08/01/1992 - "The most common neurometabolic disorders to be considered are organic acidurias and amino acid apathies followed by urea cycle disorders, congenital lactic acidosis, peroxisomal disorders, and, less frequently, sphingolipidoses, mucopolysaccharidoses, glycoprotein degradation disorders, fatty acid oxidation disorders, and neuronal ceroid lipofuscinoses." 09/01/1995 - "Recent studies in a cell-free system of human skin fibroblasts support the hypothesis that alteration of PKC activity may represent the functional link between accumulation of sphingolipids and fatty acyl-CoA esters, and perturbation of cell function in sphingolipidoses and fatty acid oxidation defects, respectively. "

Therapies and Procedures

1.	Therapeutics 03/01/2022 - "Gene and substrate reduction therapies, both of which act directly on sphingolipidosis are entering clinical trials for treatment of these disorders. " 11/24/2019 - "Advances in Sphingolipidoses: CRISPR-Cas9 Editing as an Option for Modelling and Therapy." 01/01/2019 - "Timely diagnosis of this specific sphingolipidosis while the kidneys still function normally can lead to prompt initiation of therapy and improve outcome." 01/01/2015 - "A new therapy based on substrate synthesis reduction in sphingolipidoses is showing promise. " 08/01/2014 - "For most of the sphingolipidoses, little is known about the molecular mechanisms that lead to disease, which has negatively impacted attempts to develop therapies for these devastating human diseases. "
2.	Transplantation 02/11/2023 - "In this review, we discuss gene therapy approaches for sphingolipidoses that are currently being investigated in clinical trials, among which adeno-associated viral vector-based approaches and transplantation of hematopoietic stem cells genetically modified with lentiviral vectors seem to be the most effective." 07/01/1993 - "The effects of congenic hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) after graded doses of busulfan (BU), a myeloablative but nonimmunosuppressive alkylating agent, were evaluated in the twitcher mouse model of human galactosylceramidase deficiency, a demyelinating sphingolipid storage disease. "
3.	Enzyme Replacement Therapy 01/01/1976 - "Enzyme replacement therapy for the sphingolipidoses." 05/15/1995 - "Since 3 years there is an effective enzyme replacement therapy for patients with Gaucher's disease which is the most prevalent sphingolipid storage disease. "
4.	Cell Transplantation 03/01/1991 - "We evaluated the effectiveness of administration of high-dose busulfan (BU), an alkylating agent with substantial myeloablative but negligible immunosuppressive properties, on the engraftment of congenic normal bone marrow and spleen cells (hematopoietic cell transplantation; HCT) in murine galactosylceramidase deficiency (the twitcher mouse), a model of human sphingolipid storage disease. " 07/01/1993 - "The effects of congenic hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) after graded doses of busulfan (BU), a myeloablative but nonimmunosuppressive alkylating agent, were evaluated in the twitcher mouse model of human galactosylceramidase deficiency, a demyelinating sphingolipid storage disease. "
5.	Lasers (Laser) 04/01/2002 - "Application of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry for analysis of sphingolipids in cultured skin fibroblasts from sphingolipidosis patients." 08/06/1999 - "Application of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry for analysis of sphingolipids in tissues from sphingolipidosis patients." 04/01/2002 - "Using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS), we analyzed sphingolipids in cultured skin fibroblasts from patients with sphingolipidoses, including: (a) Farber disease (FD, acid ceramidase deficiency); (b) Gaucher disease (GD); (c) Niemann-Pick disease type C (NPDC); and (d) GM1-gangliosidosis (GM1G). " 08/06/1999 - "We analyzed sphingolipids in tissues from patients with sphingolipidosis, including Farber disease (FD, acid ceramidase deficiency), Gaucher disease (GD), Niemann-Pick disease type C (NPDC), and GM1-gangliosidosis (GM1G), using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS). "