Gangliosidoses, GM2
Gangliosidoses
Sandhoff Disease
beta-Hexosaminidase beta Chain
Hexosaminidase B
G(M2) Ganglioside
Gangliosidosis, GM1
Hexosaminidase A
Tay-Sachs Disease
beta-N-Acetylhexosaminidases
Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of glycosphingolipids including gangliosides. (1/82)
Long chain base compositions of gangliosides containing mainly stearic acid could be determined without any chemical modification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry with delayed ion extraction (DE MALDI-TOF MS). The analytical results for the long chain base compositions of various samples of GM1 from the brain tissues of patients with different diseases at different ages confirmed that the proportion of d20:1 (icosasphingosine) and d20 (icosa-sphinganine) of the total sphingosine bases increased quickly until adolescent or adult age and then remained constant slightly exceeding 50%; this value was evidently higher than the proportion of d20:1 and d20 of GM1 in various adult mammalian brains. A long chain base composition of GM1 from the brain tissue of a patient with infantile type of GM1-gangliosidosis at 4y2m was abnormal and so was in two sibling patients with Spielmeyer-Vogt type of juvenile amaurotic idiocy at 19y and 21y in spite of that in the latter there was no accumulation of GM1 in the brain tissue. On the other hand, a patient with adult type of GM1 gangliosidosis at 66y showed a local accumulation of GM1 in the putamen and caudate nucleus, but its long chain base composition was found to be normal. It was of interest that the white matter of Eker rat with hereditary renal carcinoma contained a large amount of plasmalocerebroside as compared with the amount of cerebroside and sphingomyelin. The individual molecular species of plasmalocerebroside were identified by DE MALDI-TOF MS. (+info)Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. (2/82)
The residual hexosaminidase isoenzymes in juvenile Sandhoff and infantile Sandhoff disease fibroblasts, have been determined by starch gel electrophoresis and column isoelectric focusing. Hex A and hex S are the major residual isozymes in fibroblasts from the juvenile patient, while hex B is barely detectable. Only hex S could be detected in fibroblasts from infantile Sandhoff patients. These results suggest that the defects in juvenile and infantile Sandhoff disease may be different allelic modifications of the beta subunit common to hex A and hex B. (+info)Radial and linear thin-layer chromatographic prodedures compared for screening urines to detect oligosaccharidoses. (3/82)
We describe a circular (radial) thin-layer chromatographic procedure for separating urinary oligosaccharides. Results were better than those obtained by a single linear development. Bands and specific patterns were finely resolved for various known oligosaccharidoses. The procedure provides a simple means of screening for these disorders. (+info)Crystallographic evidence for substrate-assisted catalysis in a bacterial beta-hexosaminidase. (4/82)
beta-Hexosaminidase, a family 20 glycosyl hydrolase, catalyzes the removal of beta-1,4-linked N-acetylhexosamine residues from oligosaccharides and their conjugates. Heritable deficiency of this enzyme results in various forms of GalNAc-beta(1,4)-[N-acetylneuraminic acid (2,3)]-Gal-beta(1,4)-Glc-ceramide gangliosidosis, including Tay-Sachs disease. We have determined the x-ray crystal structure of a beta-hexosaminidase from Streptomyces plicatus to 2.2 A resolution (Protein Data Bank code ). beta-Hexosaminidases are believed to use a substrate-assisted catalytic mechanism that generates a cyclic oxazolinium ion intermediate. We have solved and refined a complex between the cyclic intermediate analogue N-acetylglucosamine-thiazoline and beta-hexosaminidase from S. plicatus to 2.1 A resolution (Protein Data Bank code ). Difference Fourier analysis revealed the pyranose ring of N-acetylglucosamine-thiazoline bound in the enzyme active site with a conformation close to that of a (4)C(1) chair. A tryptophan-lined hydrophobic pocket envelopes the thiazoline ring, protecting it from solvolysis at the iminium ion carbon. Within this pocket, Tyr(393) and Asp(313) appear important for positioning the 2-acetamido group of the substrate for nucleophilic attack at the anomeric center and for dispersing the positive charge distributed into the oxazolinium ring upon cyclization. This complex provides decisive structural evidence for substrate-assisted catalysis and the formation of a covalent, cyclic intermediate in family 20 beta-hexosaminidases. (+info)Clathrin-dependent and -independent internalization of plasma membrane sphingolipids initiates two Golgi targeting pathways. (5/82)
Sphingolipids (SLs) are plasma membrane constituents in eukaryotic cells which play important roles in a wide variety of cellular functions. However, little is known about the mechanisms of their internalization from the plasma membrane or subsequent intracellular targeting. We have begun to study these issues in human skin fibroblasts using fluorescent SL analogues. Using selective endocytic inhibitors and dominant negative constructs of dynamin and epidermal growth factor receptor pathway substrate clone 15, we found that analogues of lactosylceramide and globoside were internalized almost exclusively by a clathrin-independent ("caveolar-like") mechanism, whereas an analogue of sphingomyelin was taken up approximately equally by clathrin-dependent and -independent pathways. We also showed that the Golgi targeting of SL analogues internalized via the caveolar-like pathway was selectively perturbed by elevated intracellular cholesterol, demonstrating the existence of two discrete Golgi targeting pathways. Studies using SL-binding toxins internalized via clathrin-dependent or -independent mechanisms confirmed that endogenous SLs follow the same two pathways. These findings (a) provide a direct demonstration of differential SLs sorting into early endosomes in living cells, (b) provide a "vital marker" for endosomes derived from caveolar-like endocytosis, and (c) identify two independent pathways for lipid transport from the plasma membrane to the Golgi apparatus in human skin fibroblasts. (+info)The gangliosidoses: comparative features and research applications. (6/82)
Ganglioside storage diseases are inherited defects of lysosomal hydrolases that result in intralysosomal accumulation of gangliosides and other complex metabolites. Gangliosidoses occur in man, cats, cattle, dogs and swine. In all species, these diseases are characterized clinically by relentlessly progressive neurological deterioration. Lysosomal hypertrophy with characteristic ultrastructural inclusions occur in neurons, endothelial and other cells. Definitive diagnosis requires biochemical identification of the storage product and enzyme deficiency. Gangliosidoses in animals are important models of human lysosomal diseases and may be a significant complication in the maintenance of certain purebred stocks of domestic animals. (+info)Infantile sialidosis: a phenocopy of type 1 GM1 gangliosidosis distinguished by genetic complementation and urinary oligosaccharides. (7/82)
A clinical description of an apparently classical case of type 1 GM1 gangliosidosis is presented. The patient was the first-born child of first cousins. She was diagnosed at 6 weeks and died at 6 months. beta-Galactosidase activity was deficient in cultured fibroblasts using [3H]GM1 ganglioside and [3H]ceramide-lactose as substrates. Genetic complementation studies performed after cell fusion between cultured fibroblasts from the patient and from two other type 1, one type 2, and one juvenile GM1 gangliosidosis strain were positive with all strains. Subsequent studies revealed an increased excretion of a sialic acid-containing hexasaccharide in the patient's cells. Parents' fibroblasts contained normal levels of beta-galactosidase. The case emphasizes the variability of the clinical expression in sialidosis and the importance of demonstrating a primary gene defect in establishing a diagnosis of an inborn error or metabolism. (+info)Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. (8/82)
Mouse models of the GM2 gangliosidoses [Tay-Sachs, late onset Tay-Sachs (LOTS), Sandhoff] and GM1 gangliosidosis have been studied to determine whether there is a common neuro-inflammatory component to these disorders. During the disease course, we have: (i) examined the expression of a number of inflammatory markers in the CNS, including MHC class II, CD68, CD11b (CR3), 7/4, F4/80, nitrotyrosine, CD4 and CD8; (ii) profiled cytokine production [tumour necrosis factor alpha (TNF alpha), transforming growth factor (TGF beta 1) and interleukin 1 beta (IL1 beta)]; and (iii) studied blood-brain barrier (BBB) integrity. The kinetics of apoptosis and the expression of Fas and TNF-R1 were also assessed. In all symptomatic mouse models, a progressive increase in local microglial activation/expansion and infiltration of inflammatory cells was noted. Altered BBB permeability was evident in Sandhoff and GM1 mice, but absent in LOTS mice. Progressive CNS inflammation coincided with the onset of clinical signs in these mouse models. Substrate reduction therapy in the Sandhoff mouse model slowed the rate of accumulation of glycosphingolipids in the CNS, thus delaying the onset of the inflammatory process and disease pathogenesis. These data suggest that inflammation may play an important role in the pathogenesis of the gangliosidoses. (+info)GM2 gangliosidoses are a group of inherited metabolic disorders caused by the accumulation of harmful amounts of GM2 gangliosides in the body's cells, particularly in the nerve cells of the brain. There are three main types of GM2 gangliosidoses: Tay-Sachs disease, Sandhoff disease, and AB variant of GM2 gangliosidosis. These conditions are characterized by progressive neurological degeneration, which can lead to severe physical and mental disabilities, and ultimately death in childhood or early adulthood.
The underlying cause of GM2 gangliosides is a deficiency in the enzyme hexosaminidase A (Tay-Sachs and AB variant) or both hexosaminidase A and B (Sandhoff disease), which are responsible for breaking down GM2 gangliosides. Without sufficient enzyme activity, GM2 gangliosides accumulate in the lysosomes of cells, leading to cell dysfunction and death.
Symptoms of GM2 gangliosidoses can vary depending on the specific type and severity of the disorder, but often include developmental delay, muscle weakness, loss of motor skills, seizures, blindness, and dementia. There is currently no cure for GM2 gangliosidoses, and treatment is focused on managing symptoms and improving quality of life.
Gangliosidoses are a group of inherited metabolic disorders caused by the accumulation of certain complex lipids called gangliosides in the brain and nervous system. This buildup is due to a deficiency of specific enzymes needed to break down these substances. The three main types of gangliosidoses are:
1. Type 1 - Infantile Neurovisceral or Tay-Sachs Disease: Characterized by the absence of the enzyme hexosaminidase A, leading to severe neurological symptoms such as muscle weakness, blindness, and developmental delay in early infancy, with rapid progression and death usually occurring before age 4.
2. Type 2 - Juvenile or Subacute GM1 Gangliosidosis: Caused by a deficiency of the enzyme beta-galactosidase, resulting in progressive neurological symptoms such as motor and cognitive decline, beginning between ages 6 months and 2 years. Affected individuals may survive into adolescence or early adulthood.
3. Type 3 - Adult or Chronic GM1 Gangliosidosis: Characterized by a deficiency of beta-galactosidase, leading to milder neurological symptoms that appear in late childhood, adolescence, or even adulthood. The progression is slower compared to the other types, and life expectancy varies widely.
Gangliosidoses are autosomal recessive disorders, meaning an individual must inherit two copies of the defective gene (one from each parent) to develop the condition.
Sandhoff disease is a rare inherited disorder that affects the nervous system. It's a type of GM2 gangliosidosis, which is a group of conditions characterized by the body's inability to break down certain fats (lipids) called gangliosides.
In Sandhoff disease, deficiencies in the enzymes hexosaminidase A and B lead to an accumulation of GM2 ganglioside in various cells, particularly in nerve cells of the brain. This accumulation results in progressive damage to the nervous system.
The symptoms of Sandhoff disease typically appear between 6 months and 2 years of age and can include developmental delay, seizures, an exaggerated startle response, muscle weakness, loss of motor skills, and vision and hearing loss. The condition is often fatal by around age 3. It's caused by mutations in the HEXB gene, and it's inherited in an autosomal recessive manner, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the disease.
Beta-Hexosaminidase beta chain is a subunit of the beta-Hexosaminidase enzyme, which is responsible for breaking down complex lipids called gangliosides in the body. Specifically, it helps to break down a type of ganglioside called GM2 ganglioside into simpler components. Defects in this enzyme can lead to a group of genetic disorders known as the GM2 gangliosidoses, which include Tay-Sachs disease and Sandhoff disease. These conditions are characterized by the accumulation of GM2 gangliosides in various tissues, particularly in the nervous system, leading to progressive neurological deterioration.
Hexosaminidase B is a type of enzyme that is involved in the breakdown of complex lipids called gangliosides in the body. These enzymes are found in lysosomes, which are structures inside cells that break down and recycle various materials.
Hexosaminidase B specifically helps to break down a particular type of ganglioside called GM2 ganglioside, which is abundant in the nervous system. Mutations in the gene that provides instructions for making this enzyme can lead to a condition called Tay-Sachs disease, which is characterized by the accumulation of GM2 gangliosides in the nerve cells, leading to progressive neurological deterioration.
In summary, Hexosaminidase B is an essential enzyme for breaking down certain types of lipids in the body, and its deficiency can lead to serious health consequences.
GM1 gangliosidosis is a rare inherited lysosomal storage disorder caused by the deficiency of an enzyme called β-galactosidase. This enzyme is responsible for breaking down certain complex fats (gangliosides) in the body. When this enzyme is lacking or not working properly, these gangliosides accumulate in various cells, particularly in nerve cells of the brain, leading to progressive neurological deterioration.
The condition can present at different ages and with varying severity, depending on the amount of functional β-galactosidase enzyme activity. The three main types of GM1 gangliosidosis are:
1. Early infantile (type I): This is the most severe form, with symptoms appearing within the first few months of life. Infants may appear normal at birth but then develop rapidly progressing neurological problems such as developmental delay, muscle weakness, seizures, and cherry-red spots in the eyes. Life expectancy is typically less than 2 years.
2. Late infantile/juvenile (type II): Symptoms begin between ages 1 and 3 years or later in childhood. Affected individuals may have developmental delay, motor difficulties, muscle weakness, and cognitive decline. Some individuals with this form may also develop corneal clouding and bone abnormalities.
3. Adult/chronic (type III): This is the least severe form of GM1 gangliosidosis, with symptoms appearing in late childhood, adolescence, or adulthood. Symptoms can include neurological problems such as muscle weakness, tremors, and difficulties with coordination and speech.
Currently, there is no cure for GM1 gangliosidosis, and treatment is primarily supportive to manage symptoms and improve quality of life.
Hexosaminidase A is an enzyme that is responsible for breaking down certain complex molecules in the body, specifically gangliosides. This enzyme is composed of two subunits, alpha and beta, which are encoded by the genes HEXA and HEXB, respectively.
Deficiency or mutation in the HEXA gene can lead to a genetic disorder called Tay-Sachs disease, which is characterized by an accumulation of gangliosides in the nerve cells, leading to progressive neurological degeneration. The function of hexosaminidase A is to break down these gangliosides into simpler molecules that can be eliminated from the body. Without sufficient levels of this enzyme, the gangliosides build up and cause damage to the nervous system.
Tay-Sachs Disease is a rare, inherited autosomal recessive disorder that affects the nervous system's functioning. It results from the deficiency of an enzyme called hexosaminidase A (Hex-A), which is necessary for breaking down gangliosides, a type of fatty substance found in nerve cells. When Hex-A is absent or insufficient, gangliosides accumulate abnormally in the nerve cells, leading to their progressive destruction and severe neurological deterioration.
The classic infantile form of Tay-Sachs Disease manifests within the first six months of life with symptoms such as loss of motor skills, seizures, paralysis, dementia, blindness, and eventually death, usually by age four. Late-onset forms of the disease also exist, which may present in childhood or adulthood with milder symptoms.
Tay-Sachs Disease is more prevalent among individuals of Ashkenazi Jewish, French Canadian, and Cajun descent. Genetic counseling and prenatal testing are recommended for couples at risk of passing on the disease.
Beta-N-Acetylhexosaminidases are a group of enzymes that play a role in the breakdown and recycling of complex carbohydrates in the body. Specifically, they help to break down gangliosides, which are a type of molecule found in cell membranes.
There are several different isoforms of beta-N-Acetylhexosaminidases, including A, B, and S. These isoforms are formed by different combinations of subunits, which can affect their activity and substrate specificity.
Mutations in the genes that encode for these enzymes can lead to a variety of genetic disorders, including Tay-Sachs disease and Sandhoff disease. These conditions are characterized by an accumulation of gangliosides in the brain, which can cause progressive neurological deterioration and death.
Treatment for these conditions typically involves managing symptoms and providing supportive care, as there is currently no cure. Enzyme replacement therapy has been explored as a potential treatment option, but its effectiveness varies depending on the specific disorder and the age of the patient.
GM2 gangliosidoses
GM1 gangliosidoses
Gangliosidosis
GM 2 gangliosidosis
GM2-gangliosidosis, AB variant
History of Tay-Sachs disease
Tay-Sachs disease
GLB1
GM1
GM2A
HEXB
HEXA
List of OMIM disorder codes
Sphingolipidoses
Jacob sheep
Sweat gland
GM2 (ganglioside)
Dysesthesia
Cathepsin A
Sio Gene Therapies
Portuguese Water Dog
Sandhoff disease
Christine Ann Denny
Lipid storage disorder
Migalastat
Cherry-red spot
Mucolipidosis
Burmese cat
Glycosphingolipid
Niemann-Pick disease, type C
GM2 gangliosidoses - Wikipedia
GM1 gangliosidosis: MedlinePlus Genetics
GM1 Gangliosidosis: Background, Pathophysiology, Epidemiology
Myelin abnormalities in the optic and sciatic nerves in mice with GM1-gangliosidosis
Recursion falls after delay for GM2 gangliosidosis trial (NASDAQ:RXRX) | Seeking Alpha
Identification of Two Novel Pathogenic Mutations of GM1 Gangliosidosis in Japanese Domestic Shorthair Cats - WSAVA 2015...
Gene therapy for GM1 gangliosidosis: challenges of translational medicine. - Department of Experimental Psychology
Generalized Gangliosidoses | Signs, Symptoms, Support
Gangliosidosis (GM 1/GM 2)
GM1 Gangliosidosis: Background, Pathophysiology, Epidemiology
GM1 Gangliosidosis - United Brain Association
Hyperphosphatasemia in GM1 gangliosidosis.<...
Account | Gangliosidosis GM2 | DNA tests for your pets
Critical role of iron in the pathogenesis of the murine gangliosidoses. - Immunology
GM1-Gangliosidosis typ I-II, differential diagnosis | Amedes Genetics
GM1 Gangliosidosis Treatment Market trends - Article Wood - Bloggers Unite India
Improvements in Developmental Milestones Observed With GM1 Gangliosidosis Gene Therapy
GM2-Gangliosidosis Variant AB via the GM2A Gene Test - PreventionGenetics
Critical role of iron in the pathogenesis of the murine gangliosidoses. - Department of Pharmacology
Robert V. Farese | Academic Profile | Harvard T.H. Chan School of Public Health
Lipid Storage Diseases | National Institute of Neurological Disorders and Stroke
Canine GM|sub|1|/sub| gangliosidosis: An Ultrastructural and Biochemical Study - Fingerprint - Mayo Clinic
6:53 am
Find NINDS Clinical Trials | National Institute of Neurological Disorders and Stroke
Passage Bio Reports Positive Interim Clinical Data from Study of First Eight Patients with GM1 Gangliosidosis - Global Genes
ICGNMD Publications | International Centre for Genomic Medicine in Neuromuscular Diseases - UCL - University College London
Azafaros Announces Enrollment of First Patient in Phase 2 RAINBOW Study Evaluating AZ-3102 in GM2 and NP-C Patients - DutchNews...
magnetic resonance imaging and pathological characteristics. GM2 gangliosidosis (B variant) in two Japanese Chins: clinical -...
GLB14
- Variants (also called mutations) in the GLB1 gene cause GM1 gangliosidosis. (medlineplus.gov)
- GM1 gangliosidosis is a fatal, progressive, neurodegenerative lysosomal storage disease caused by mutations in the β-galactosidase ( GLB1 ) gene. (vin.com)
- GM1 gangliosidosis is caused by an abnormal variation (mutation) in the GLB1 gene, which plays a role in producing beta-galactosidase. (unitedbrainassociation.org)
- GLB1-related conditions including GM1-gangliosidosis and mucopolysaccharidosis type IVB (MPSIVB) are two distinct lysosomal storage disorders caused by mutations the GLB1 gene. (jewishgenetics.org)
Deficiency6
- The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. (wikipedia.org)
- Deficiency of the lysosomal hydrolase, acid β -galactosidase, causes G M1 gangliosidosis and Morquio disease type B (ie, mucopolysaccharidosis type IVB ). (medscape.com)
- GM1 gangliosidosis is due to an inherited deficiency of the enzyme beta-galactosidase, whereas GM2 gangliosidosis is caused by a lack of the enzyme beta-hexosaminidase. (labogen.com)
- Suzuki Y, Oshima A, Nanba E. B-Galactosidase deficiency (B-Galactosidosis): GM1 gangliosidosis and Morquio B disease. (medscape.com)
- GM1 gangliosidosis is caused by a deficiency of an enzyme called beta-galactosidase. (unitedbrainassociation.org)
- Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis. (harvard.edu)
Variant4
- GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. (wikipedia.org)
- GM2-Gangliosidosis variant AB, also known as Tay-Sachs disease AB Variant, is the rarest form of GM2-gangliosidoses. (preventiongenetics.com)
- GM2-Gangliosidosis variant AB is inherited in an autosomal recessive manner and results from pathogenic variants in the GM2A gene (Schröder et al. (preventiongenetics.com)
- GM2 gangliosidosis (B variant) in two Japanese Chins: clinical, magnetic resonance imaging and pathological characteristics. (tamu.edu)
Onset4
- Except in some rare, late-onset forms, the GM2 gangliosidoses are fatal. (wikipedia.org)
- GM1 gangliosidosis is usually classified as one of three different types depending on the age of onset. (unitedbrainassociation.org)
- Type IIa (Late Onset) Infantile GM1 Gangliosidosis (GM1). (cgtlive.com)
- The differential diagnosis includes Canavan disease, alexander disease, and infantile-onset GM2 gangliosidosis. (eurorad.org)
Sandhoff8
- There are no authorized therapies for the treatment of the GM2 Gangliosidosis (Tay-Sachs and Sandhoff disease). (wikipedia.org)
- N-Acetyl-Leucine has been granted multiple orphan drug designations from the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA) and the European Medicines Agency (EMA) for the treatment of a various genetic diseases, including GM2 Gangliosidosis (Tay-Sachs and Sandhoff). (wikipedia.org)
- Compassionate use studies in both Tay-Sachs and Sandhoff patients have demonstrated the positive clinical effects of treatment with N-Acetyl-Leucine for GM2 Gangliosidosis These studies further demonstrated that the treatment is well tolerated, with a good safety profile. (wikipedia.org)
- citation needed] A multinational clinical trial investigating N-Acetyl-L-Leucine for the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff) began in 2019 Recruitment is ongoing. (wikipedia.org)
- GM1 gangliosidosis is similar to Tay-Sachs disease and Sandhoff disease, but the disorders are caused by different gene mutations and enzyme deficiencies. (unitedbrainassociation.org)
- They all presented with the acute form of GM2 gangliosidosis, which is clinically undistinguishable from the classical acute forms of Tay-Sachs and Sandhoff phenotypes (Gravel 2001). (preventiongenetics.com)
- In 2022, the compound received Fast Track Designation for GM1 and GM2 gangliosidoses as well as NP-C and Orphan Drug Designations (ODD) for GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NP-C from the FDA. (dutchnews.nl)
- GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides, respectively, in the central nervous system (CNS), resulting in progressive and severe neurological impairment and early death. (dutchnews.nl)
Autosomal recessive2
- G M1 gangliosidosis is an autosomal recessive lysosomal storage disorder characterized by the generalized accumulation of G M1 ganglioside, oligosaccharides, and the mucopolysaccharide keratan sulfate (and their derivatives). (medscape.com)
- All 3 types of G M1 gangliosidosis are inherited as autosomal recessive traits and have equal sex distributions. (medscape.com)
Disorders4
- Conditions like GM1 gangliosidosis that cause molecules to build up inside lysosomes are called lysosomal storage disorders. (medlineplus.gov)
- GM1 gangliosidosis is one of a group of diseases called lysosomal storage disorders. (unitedbrainassociation.org)
- Azafaros is developing the compound as a potentially disease-modifying treatment in severe metabolic disorders including GM1 and GM2 gangliosidoses and NP-C. Enrollment of the first patient in the study is an important milestone for Azafaros in its mission to bring new treatment options to these patients and their families. (dutchnews.nl)
- AZ-3102 is an orally available azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick disease type C (NP-C). (dutchnews.nl)
Lysosomes1
- The gangliosidoses are progressive, fatal neurological diseases of cats, humans and other animals where gangliosides accumulate principally in neuronal lysosomes. (labogen.com)
Gene3
- Gene therapy for GM1 gangliosidosis: challenges of translational medicine. (ox.ac.uk)
- New data from the ongoing Imagine-1 clinical trial (NCT04713475) demonstrate good safety and impressive improvements in clinically meaningful end points in patients with GM1 gangliosidosis treated with PBGM01, an investigational gene therapy from Passage Bio. (cgtlive.com)
- Imagine-1 is a phase 1/2, global, open-label, dose-escalation study of the AAVhu68 gene therapy PBGM01 delivered by intra-cisterna magna (ICM) injection in six cohorts of pediatric subjects with early and late infantile GM1 Gangliosidosis (GM1). (globalgenes.org)
Fatal2
- The gangliosidoses are progressive, fatal neurological diseases of cats where gangliosides. (labogen.com)
- Although both types of gangliosidoses cause fatal progressive brain disease, they are caused by entirely different genetic errors of two different lysosomal enzymes. (labogen.com)
Disease9
- The current standard of care for GM2 Gangliosidosis disease is limited to supportive care and aimed at providing adequate nutrition and hydration. (wikipedia.org)
- The US FDA has granted IntraBio a Rare Pediatric Disease Designation for N-Acetyl-Leucine for the treatment of GM2 Gangliosidosis. (wikipedia.org)
- GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. (nih.gov)
- Two and a half years ago, we were faced with her diagnosis of GM1 gangliosidosis, a rare degenerative neurological disease. (themighty.com)
- GM1 gangliosidosis is a progressive, degenerative brain and central nervous system disease. (unitedbrainassociation.org)
- The early signs of GM1 gangliosidosis disease vary from case to case, and different forms of the disease have various initial symptoms. (unitedbrainassociation.org)
- Gangliosidosis, also known as lysosomal storage disease , is a genetic condition that occurs when Korats don't have the enzymes to properly run their nervous system. (cyberpet.com)
- The clinical trial is being conducted in Brazil and the US and will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics across two doses of its lead asset, AZ-3102, in patients with GM2 gangliosidosis and Niemann-Pick disease type C (NP-C). (dutchnews.nl)
- We remain focused on execution across our ongoing clinical programs and are excited to have dosed additional patients in our Imagine-1 trial for GM1 gangliosidosis as well as the first patient in our GALax-C trial for infantile Krabbe disease," said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. (biospace.com)
Infantile form2
- The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually develop by the age of 6 months. (medlineplus.gov)
- The infantile form of G M1 gangliosidosis (type 1) typically presents between birth and age 6 months with progressive organomegaly, dysostosis multiplex, facial coarsening, and rapid neurologic deterioration within the first year of life. (medscape.com)
Profound intellectual disability1
- GM1 gangliosidoses causes skeletal abnormalities, seizures, loss of vision and profound intellectual disability. (themighty.com)
Diseases1
- Neurodegeneration is a prominent feature of the gangliosidoses, a group of lysosomal storage diseases. (ox.ac.uk)
Pathological1
- There are several possible mechanisms by which the gangliosidoses may cause their pathological hallmarks. (medscape.com)
Inherited disorder1
- GM1 gangliosidosis is an inherited disorder that destroys nerve cells (neurons) in the brain and spinal cord. (medlineplus.gov)
Genetic disorder2
- The shares of the clinical-stage biotechnology company Recursion Pharmaceuticals ( RXRX -10.2% ) are set to close at an all-time low on Thursday after the company announced a delay for its Phase 2 trial for REC-3599 in rare genetic disorder, infantile GM2 gangliosidosis (GM). (seekingalpha.com)
- Generalized gangliosidoses, or GM1 gangliosidosis, is a genetic disorder that results in the progressive destruction of neurons in the brain and spinal cord. (themighty.com)
Symptoms4
- However, the signs and symptoms of these three types can overlap, leading some researchers to believe that GM1 gangliosidosis occurs on a spectrum instead of as three distinct types. (medlineplus.gov)
- The age at which symptoms first appear varies in people with GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. (medlineplus.gov)
- Damage caused by the buildup of GM1 ganglioside leads to the destruction of neurons, causing many of the signs and symptoms of GM1 gangliosidosis. (medlineplus.gov)
- In general, people with GM1 gangliosidosis have milder signs and symptoms if they have higher levels of functional β-galactosidase activity. (medlineplus.gov)
Clinical2
- Brunetti-Pierri N, Scaglia F. GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. (medscape.com)
- Toy Poodle and Shiba Inu dogs affected with GM2- gangliosidosis develop nervous system clinical signs including vision loss, walking difficulties, loss of balance, tremors, cerebellar ataxia, decreased appetit and vomiting. (eurovetgene.com)
Brain1
- Here we show altered iron homeostasis in mouse models of both GM1 and GM2 gangliosidoses, which are characterized by progressive depletion of iron in brain tissue. (ox.ac.uk)
Mutations2
- In this study, we successfully identified the two novel pathogenic mutations in feline GM1 gangliosidosis. (vin.com)
- There are 2 main types of GM2 gangliosidosis, each of which can be caused by numerous different mutations. (msdmanuals.com)
Mice2
- We found that key regulators of iron homeostasis, hepcidin and IL-6, were increased in gangliosidoses mice. (ox.ac.uk)
- Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice. (wikigenes.org)
Patients2
- Enzyme activity is markedly reduced in patients with G M1 gangliosidosis. (medscape.com)
- A high frequency of G M1 gangliosidosis has been reported from Southern Brazil, and a large number of Japanese patients with the adult form have been reported. (medscape.com)
Type5
- GM1 gangliosidosis type II occurs in one of two forms: the late infantile or the juvenile forms. (medlineplus.gov)
- Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, coarse facial features, or enlarged organs. (medlineplus.gov)
- GM1 gangliosidosis type III is the adult or chronic form of the condition, and this is the mildest form. (medlineplus.gov)
- Life expectancy varies among people with GM1 gangliosidosis type III. (medlineplus.gov)
- Inheritance of GM1 gangliosidosis appears to be type-specific. (unitedbrainassociation.org)
Early2
- This form of G M1 gangliosidosis most frequently presents in early infancy and may be evident at birth. (medscape.com)
- Life expectancy in those with GM1 gangliosidoses is usually early childhood. (themighty.com)
Rare2
- G M1 gangliosidosis is a rare disorder, and data concerning incidence are not widely available. (medscape.com)
- GM1 gangliosidosis is a rare condition that causes the progressive degeneration of elements of the central nervous system. (unitedbrainassociation.org)
Types1
- There are two types of gangliosidoses, GM1 and GM2 gangliosidosis. (labogen.com)
Cats1
- Recently, two different families of feline GM1 gangliosidosis caused by each different novel mutation were found in Japanese domestic shorthair cats. (vin.com)
Treatment1
- Global GM1 Gangliosidosis Treatment market is poised to value over USD 447.8 million by 2028 end at a CAGR of over 36% during the forecast period 2021 to 2028. (articlewood.com)
Research1
- Dive into the research topics of 'Hyperphosphatasemia in GM1 gangliosidosis. (vub.be)
Condition1
- GM1 gangliosidosis is an inherited condition. (unitedbrainassociation.org)