Mucopolysaccharidosis VII
Mucopolysaccharidoses
Glucuronidase
Mucopolysaccharidosis I
Mucopolysaccharidosis VI
Mucopolysaccharidosis III
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Iduronidase
Glycosaminoglycans
N-Acetylgalactosamine-4-Sulfatase
Genetic Therapy
Lysosomes
Chondro-4-Sulfatase
Iduronate Sulfatase
Chondroitinsulfatases
Enzyme Replacement Therapy
Dogs
Factor VII
Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus. (1/91)
Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a genetic deficiency of beta-glucuronidase (GUS). We used a recombinant adeno-associated virus vector (AAV-GUS) to deliver GUS cDNA to MPS VII mice. The route of vector administration had a dramatic effect on the extent and distribution of GUS activity. Intramuscular injection of AAV-GUS resulted in high, localized production of GUS, while intravenous administration produced low GUS activity in several tissues. This latter treatment of MPS VII mice reduced glycosaminoglycan levels in the liver to normal and reduced storage granules dramatically. We show that a single administration of AAV-GUS can provide sustained expression of GUS in a variety of cell types and is sufficient to reverse the disease phenotype at least in the liver. (+info)Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease. (2/91)
For many inborn errors of metabolism, early treatment is critical to prevent long-term developmental sequelae. We have used a gene-therapy approach to demonstrate this concept in a murine model of mucopolysaccharidosis type VII (MPS VII). Newborn MPS VII mice received a single intravenous injection with 5.4 x 10(6) infectious units of recombinant adeno-associated virus encoding the human beta-glucuronidase (GUSB) cDNA. Therapeutic levels of GUSB expression were achieved by 1 week of age in liver, heart, lung, spleen, kidney, brain, and retina. GUSB expression persisted in most organs for the 16-week duration of the study at levels sufficient to either reduce or prevent completely lysosomal storage. Of particular significance, neurons, microglia, and meninges of the central nervous system were virtually cleared of disease. In addition, neonatal treatment of MPS VII mice provided access to the central nervous system via an intravenous route, avoiding a more invasive procedure later in life. These data suggest that gene transfer mediated by adeno-associated virus can achieve therapeutically relevant levels of enzyme very early in life and that the rapid growth and differentiation of tissues does not limit long-term expression. (+info)Systemic and central nervous system correction of lysosomal storage in mucopolysaccharidosis type VII mice. (3/91)
Mucopolysaccharidosis (MPS) type VII patients lack functional beta-glucuronidase, leading to systemic and central nervous system dysfunction. In this study we tested whether recombinant adenovirus that encodes beta-glucuronidase (Adbetagluc), delivered intravenously and into the brain parenchyma of MPS type VII mice, could provide long-term transgene expression and correction of lysosomal distension. We also tested whether systemic treatment with the immunosuppressive anti-CD40 ligand antibody, MR-1, affected transgene expression. We found substantial plasma beta-glucuronidase activity for over 9 weeks after gene transfer in the MR-1- treated group, with subsequent decline in activity corresponding to a delayed anti-beta-glucuronidase antibody response. At 16 weeks, near wild-type amounts of beta-glucuronidase activity and striking reduction of lysosomal pathology were detected in livers from mice that had received either MR-1 cotreatment or control antibody. In the lung and kidney, beta-glucuronidase activity was markedly higher for the MR-1-treated group. beta-Glucuronidase activity in the brain persisted independently of MR-1 treatment. Activity was intense in the injected hemisphere and was also evident in the noninjected cortex and striatum, with dramatic improvements in storage deposits in areas of both hemispheres. These results indicate that prolonged enzyme expression from transgenes delivered to deficient liver and brain can mediate pervasive correction and illustrate the potential for gene therapy of MPS and other lysosomal storage diseases. (+info)Behavior and therapeutic efficacy of beta-glucuronidase-positive mononuclear phagocytes in a murine model of mucopolysaccharidosis type VII. (4/91)
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 beta-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 beta-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. (+info)Reduction of lysosomal storage in murine mucopolysaccharidosis type VII by transplantation of normal and genetically modified macrophages. (5/91)
This study examined the ability of macrophages to serve as target cells of gene therapy for mucopolysaccharidosis (MPS) type VII using a murine model. Bone marrow cells were harvested from syngeneic normal mice and differentiated to macrophages. These cells were given to nonmyeloablated MPS VII mice. After transplantation, donor cells populated the liver and spleen. The pathologic improvement at day 38 after transplantation was significant and glycosaminoglycan storage was reduced. To develop gene therapy using this system, a retroviral vector expressing human beta-glucuronidase (HBG) was used to infect macrophages cultivated from MPS VII mice and given to nonmyeloablated MPS VII mice. At 38 days after transplantation, HBG-positive cells were still observed histochemically and pathologic improvement was significant. These observations suggest that macrophage transplantation is a promising method for treatment of murine MPS VII without myeloablation, and macrophages may be good target cells for ex vivo gene therapy for MPS VII. (+info)Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII. (6/91)
The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from defective catabolism of glycosaminoglycans (GAGs). Echocardiographic abnormalities in dogs with MPS type VII (Sly syndrome, beta-glucuronidase deficiency) included mitral valve thickening and insufficiency, large aortic dimensions in both the long and short axes, and thickened aortic valves. Grossly, at post mortem examination, there was nodular thickening of the mitral valve, a prominent ductus diverticulum, and a dilated aorta with thickened walls. Histologically, cytoplasmic vacuolation was seen in cells of the mitral valves, coronary arteries, and aorta. By electron microscopy, the cells of the mitral valve were packed with electron-lucent cytoplasmic vacuoles. The mean residual activity of beta-glucuronidase in the aorta and myocardium was <1% of normal, the mean hexosaminidase A activity >2. 5 times normal, and the mean GAG concentrations more than twice normal. In three MPS VII dogs that received heterologous BMT at 6 weeks of age, the echocardiographic abnormalities were improved, and the histopathologic and ultrastructural pathology was reduced. In the aorta and myocardium, the mean beta-glucuronidase activity of the BMT group was 4.5% and 11% of normal, respectively, and the hexosaminidase A activity and GAG concentrations were normalized. Bone Marrow Transplantation (2000) 25, 1289-1297. (+info)Significantly increased expression of beta-glucuronidase in the central nervous system of mucopolysaccharidosis type VII mice from the latency-associated transcript promoter in a nonpathogenic herpes simplex virus type 1 vector. (7/91)
Herpes simplex virus (HSV) has the ability to establish life-long latent infections in postmitotic neurons and to remain transcriptionally active, continuously expressing latency-associated transcripts (LAT) while producing minimal disease. These properties have made HSV an excellent candidate for neuronal gene transfer. Previously, we have shown that in mucopolysaccharidosis type VII mice (MPS VII, beta-glucuronidase deficiency) the LAT promoter is capable of expressing beta-glucuronidase (GUSB) in the trigeminal ganglion and the brainstem after latency is established. However, the number of neurons expressing GUSB is much lower than the number expressing 2-kb LAT following a wild-type virus infection. In this study, we have evaluated the effect of the position of the coding sequence relative to the LAT promoter on beta-glucuronidase gene expression in the central nervous system (CNS). Non-neurovirulent (ICP-34.5-deleted HSV-1) vectors were used, allowing direct intracranial injection. Significantly more GUSB activity was detected in brains of MPS VII mice inoculated with a recombinant virus (HSV-LAT-GUSB-JS) in which the GUSB cDNA was inserted near the LAT promoter, compared to viruses where it was inserted farther downstream in either the LAT exon 1 or overlapping exon 1 and the 2-kb LAT intron. This vector produced more than 100 times the number of positive cells than the other constructs. During acute infection, the distribution of viral replication differed from the distribution of GUSB enzyme expression. Viral antigen was predominately present in cells around the site of injection in the caudate putamen and in ependymal cells lining the ventricles. In contrast, GUSB expression was present mainly in cells of the thalamus and hypothalamus, which did not exhibit viral antigen, suggesting that GUSB enzyme activity was expressed from latently but not acutely infected neuronal cells. This vector design should be useful for high-level expression of various genes in the CNS. (+info)Long-term and significant correction of brain lesions in adult mucopolysaccharidosis type VII mice using recombinant AAV vectors. (8/91)
Most lysosomal storage diseases, including mucopolysaccharidosis, affect the central nervous system (CNS). They often induce severe and progressive mental retardation. Replacement therapy by purified enzyme infusions is a promising approach for the treatment of peripheral organs but without effect on CNS pathology because the enzyme cannot cross the blood-brain barrier. Intracranial injection of recombinant adeno-associated virus (AAV) vectors offers an alternative for sustained local enzyme delivery from genetically engineered cells. We stereotactically injected an AAV vector containing the human beta-glucuronidase cDNA into the striatum of adult mice severely affected by mucopolysaccharidosis type VII at the time of treatment. Six weeks later, beta-glucuronidase activity in the injected hemisphere was comparable to that of heterozygous mice, which have a normal phenotype. Areas staining positive for enzyme activity enlarged with time, representing more than 10% of the hemisphere volume by 16 weeks. A complete reversion of lysosomal storage lesions was evident in these areas, as well as in most neurons located in surrounding negative areas and in the noninjected hemisphere. Thus, a single intracerebral injection of AAV vectors could achieve a broad and sustained lysosomal enzyme delivery, allowing for stable reversion of storage lesions in a significant fraction of the adult brain. (+info)Mucopolysaccharidosis (MPS) VII, also known as Sly syndrome, is a rare genetic disorder caused by the deficiency of the enzyme beta-glucuronidase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs), or mucopolysaccharides, in the body. When this enzyme is not present in sufficient amounts, GAGs accumulate in various tissues and organs, leading to progressive damage.
The symptoms of MPS VII can vary widely, but often include coarse facial features, short stature, skeletal abnormalities, hearing loss, heart problems, and intellectual disability. Some individuals with MPS VII may also have cloudy corneas, enlarged liver and spleen, and difficulty breathing due to airway obstruction. The severity of the condition can range from mild to severe, and life expectancy is often reduced in those with more severe symptoms.
MPS VII is inherited in an autosomal recessive manner, which means that an individual must inherit two copies of the mutated gene (one from each parent) in order to develop the condition. Treatment for MPS VII typically involves enzyme replacement therapy, which can help to slow down the progression of the disease and improve some symptoms. However, there is currently no cure for this condition.
Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by the deficiency of specific enzymes needed to break down complex sugars called glycosaminoglycans (GAGs or mucopolysaccharides). As a result, these GAGs accumulate in various tissues and organs, leading to progressive cellular damage and multi-organ dysfunction. There are several types of MPS, including Hurler syndrome, Hunter syndrome, Sanfilippo syndrome, Morquio syndrome, Maroteaux-Lamy syndrome, and Sly syndrome, each resulting from a deficiency in one of the eleven different enzymes involved in GAGs metabolism. The clinical presentation, severity, and prognosis vary among the types but commonly include features such as developmental delay, coarse facial features, skeletal abnormalities, hearing loss, heart problems, and reduced life expectancy.
Glucuronidase is an enzyme that catalyzes the hydrolysis of glucuronic acid from various substrates, including molecules that have been conjugated with glucuronic acid as part of the detoxification process in the body. This enzyme plays a role in the breakdown and elimination of certain drugs, toxins, and endogenous compounds, such as bilirubin. It is found in various tissues and organisms, including humans, bacteria, and insects. In clinical contexts, glucuronidase activity may be measured to assess liver function or to identify the presence of certain bacterial infections.
Mucopolysaccharidosis I (MPS I) is a rare genetic disorder caused by the deficiency of an enzyme called alpha-L-iduronidase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs), also known as mucopolysaccharides, in the body.
When the enzyme is deficient, GAGs accumulate in various tissues and organs, leading to a range of symptoms that can affect different parts of the body, including the skeletal system, heart, respiratory system, eyes, and central nervous system. There are three subtypes of MPS I: Hurler syndrome (the most severe form), Hurler-Scheie syndrome (an intermediate form), and Scheie syndrome (the least severe form).
The symptoms and severity of MPS I can vary widely depending on the specific subtype, with Hurler syndrome typically causing more significant health problems and a shorter life expectancy than the other two forms. Treatment options for MPS I include enzyme replacement therapy, bone marrow transplantation, and various supportive therapies to manage symptoms and improve quality of life.
Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a rare genetic disorder caused by the deficiency of an enzyme called N-acetylgalactosamine 4-sulfatase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs) or mucopolysaccharides, which are found in various tissues and organs throughout the body.
When the enzyme is deficient, GAGs accumulate within the lysosomes of cells, leading to cellular dysfunction and tissue damage. This accumulation results in a range of symptoms that can affect multiple organ systems, including the skeletal system, cardiovascular system, respiratory system, and central nervous system.
The signs and symptoms of MPS VI can vary widely among affected individuals, but common features include: coarse facial features, short stature, stiff joints, restricted mobility, recurrent respiratory infections, hearing loss, heart valve abnormalities, and clouding of the cornea. The severity of the disease can range from mild to severe, and life expectancy is generally reduced in individuals with more severe forms of the disorder.
MPS VI is inherited as an autosomal recessive trait, which means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.
Mucopolysaccharidosis III, also known as Sanfilippo syndrome, is a genetic disorder caused by the deficiency of specific enzymes needed to break down complex sugar molecules called glycosaminoglycans (GAGs) or mucopolysaccharides. This results in an accumulation of these substances in various tissues and organs, leading to progressive damage.
There are four main types of Mucopolysaccharidosis III (A, B, C, and D), each caused by a deficiency in one of the following enzymes: heparan N-sulfatase (type A), alpha-N-acetylglucosaminidase (type B), acetyl-CoAlpha-glucosaminide acetyltransferase (type C), or N-acetylglucosamine 6-sulfatase (type D).
The symptoms of Mucopolysaccharidosis III typically become apparent between the ages of 2 and 6, and may include developmental delays, hyperactivity, behavioral problems, sleep disturbances, coarse facial features, hirsutism, hepatosplenomegaly (enlarged liver and spleen), and joint stiffness. Over time, individuals with Mucopolysaccharidosis III may experience a decline in cognitive abilities, loss of previously acquired skills, and mobility issues.
Currently, there is no cure for Mucopolysaccharidosis III, and treatment is focused on managing the symptoms and improving quality of life. Enzyme replacement therapy, gene therapy, and stem cell transplantation are some of the experimental treatments being investigated for this condition.
Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare X-linked recessive genetic disorder caused by the deficiency of an enzyme called iduronate sulfatase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs) or mucopolysaccharides in the body.
When this enzyme is missing or not functioning properly, GAGs accumulate in various tissues and organs, leading to progressive cellular damage and organ dysfunction. The symptoms of MPS II can vary widely but often include developmental delays, coarse facial features, hearing loss, airway obstruction, heart problems, enlarged liver and spleen, and joint stiffness.
The severity of the disease can range from mild to severe, with some individuals experiencing only moderate symptoms while others may have significant intellectual disability and life-threatening complications. Treatment options for MPS II include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), but there is currently no cure for the disease.
Mucopolysaccharidosis IV (MPS IV), also known as Morquio Syndrome, is a rare genetic disorder that belongs to the family of diseases called mucopolysaccharidoses. It is characterized by the accumulation of glycosaminoglycans (GAGs or mucopolysaccharides) in various tissues and organs due to deficiencies in specific enzymes needed to break down these complex carbohydrates.
There are two types of MPS IV: Type A and Type B, which are caused by deficiencies in different enzymes (GALNS and B3GALNT1, respectively). Both types result in similar symptoms but may vary in severity. The accumulation of GAGs primarily affects the bones, cartilage, eyes, ears, heart, and respiratory system.
Common features of MPS IV include:
* Dwarfism with short trunk and long limbs
* Progressive skeletal abnormalities such as kyphosis (hunchback), scoliosis (curvature of the spine), pectus carinatum (protruding breastbone), and joint laxity or stiffness
* Coarse facial features
* Corneal clouding
* Hearing loss
* Heart valve abnormalities
* Respiratory issues
* Hypermobile and dislocated joints
* Carpal tunnel syndrome
* Spinal cord compression
Treatment for MPS IV primarily focuses on managing symptoms, improving quality of life, and preventing complications. Enzyme replacement therapy (ERT) is available for Type B but not for Type A. Other treatments may include physical therapy, surgery, and medications to address specific symptoms.
Iduronidase is a type of enzyme that helps break down complex sugars called glycosaminoglycans (GAGs) in the body. Specifically, iduronidase is responsible for breaking down a type of GAG called dermatan sulfate and heparan sulfate.
Deficiency or absence of this enzyme can lead to a genetic disorder known as Mucopolysaccharidosis Type I (MPS I), which is characterized by the accumulation of GAGs in various tissues and organs, leading to progressive damage and impairment. There are two forms of MPS I: Hurler syndrome, which is the severe form, and Scheie syndrome, which is the milder form.
Iduronidase replacement therapy is available for the treatment of MPS I, in which the missing enzyme is delivered directly to the patient's body through intravenous infusion. This helps break down the accumulated GAGs and prevent further damage to the tissues and organs.
Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units. They are a major component of the extracellular matrix and connective tissues in the body. GAGs are negatively charged due to the presence of sulfate and carboxyl groups, which allows them to attract positively charged ions and water molecules, contributing to their ability to retain moisture and maintain tissue hydration and elasticity.
GAGs can be categorized into four main groups: heparin/heparan sulfate, chondroitin sulfate/dermatan sulfate, keratan sulfate, and hyaluronic acid. These different types of GAGs have varying structures and functions in the body, including roles in cell signaling, inflammation, and protection against enzymatic degradation.
Heparin is a highly sulfated form of heparan sulfate that is found in mast cells and has anticoagulant properties. Chondroitin sulfate and dermatan sulfate are commonly found in cartilage and contribute to its resiliency and ability to withstand compressive forces. Keratan sulfate is found in corneas, cartilage, and bone, where it plays a role in maintaining the structure and function of these tissues. Hyaluronic acid is a large, nonsulfated GAG that is widely distributed throughout the body, including in synovial fluid, where it provides lubrication and shock absorption for joints.
N-Acetylgalactosamine-4-Sulfatase is an enzyme that is responsible for breaking down complex carbohydrates in the body. Its specific function is to remove a sulfate group from a particular type of sugar molecule called N-acetylgalactosamine-4-sulfate, which is found on certain proteoglycans (large, complex sugars attached to proteins) in the body.
This enzyme plays an important role in the normal functioning of cells and tissues, particularly in the development and maintenance of bones, cartilage, and other connective tissues. Deficiencies in this enzyme can lead to a rare genetic disorder called Morquio A syndrome (also known as MPS IVA), which is characterized by skeletal abnormalities, short stature, and other health problems.
Genetic therapy, also known as gene therapy, is a medical intervention that involves the use of genetic material, such as DNA or RNA, to treat or prevent diseases. It works by introducing functional genes into cells to replace missing or faulty ones caused by genetic disorders or mutations. The introduced gene is incorporated into the recipient's genome, allowing for the production of a therapeutic protein that can help manage the disease symptoms or even cure the condition.
There are several approaches to genetic therapy, including:
1. Replacing a faulty gene with a healthy one
2. Inactivating or "silencing" a dysfunctional gene causing a disease
3. Introducing a new gene into the body to help fight off a disease, such as cancer
Genetic therapy holds great promise for treating various genetic disorders, including cystic fibrosis, muscular dystrophy, hemophilia, and certain types of cancer. However, it is still an evolving field with many challenges, such as efficient gene delivery, potential immune responses, and ensuring the safety and long-term effectiveness of the therapy.
Lysosomes are membrane-bound organelles found in the cytoplasm of eukaryotic cells. They are responsible for breaking down and recycling various materials, such as waste products, foreign substances, and damaged cellular components, through a process called autophagy or phagocytosis. Lysosomes contain hydrolytic enzymes that can break down biomolecules like proteins, nucleic acids, lipids, and carbohydrates into their basic building blocks, which can then be reused by the cell. They play a crucial role in maintaining cellular homeostasis and are often referred to as the "garbage disposal system" of the cell.
Chondro-4-sulfatase is an enzyme that belongs to the family of hydrolases, specifically those acting on ester bonds in sulfuric acid esters. It is responsible for catalyzing the hydrolysis of the 4-sulfate ester group from N-acetylgalactosamine 4-sulfate residues found in chondroitin 4-sulfate, a type of glycosaminoglycan (GAG) that is abundant in connective tissues such as cartilage.
Chondroitin 4-sulfate plays important roles in the structure and function of the extracellular matrix, including regulating cell adhesion, migration, and differentiation. The action of chondro-4-sulfatase helps to control the balance between sulfated and non-sulfated GAG chains, which is critical for maintaining normal tissue homeostasis.
Defects in chondro-4-sulfatase activity can lead to a rare genetic disorder called chondrodysplasia punctata type 1B (CDPX1B), also known as multiple sulfatase deficiency (MSD). This condition is characterized by skeletal abnormalities, developmental delay, and other neurological symptoms.
Iduronate sulfatase is an enzyme that plays a crucial role in the breakdown and recycling of complex sugars called glycosaminoglycans (GAGs). These GAGs are important components of various tissues, including connective tissues, bones, and cartilage.
Iduronate sulfatase is specifically responsible for breaking down a type of GAG known as dermatan sulfate and heparan sulfate by removing sulfate groups from specific sugar molecules in these GAGs. This enzyme is located in the lysosomes, which are membrane-bound organelles within cells that break down and recycle various materials.
Deficiency of iduronate sulfatase leads to a genetic disorder called Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome. In this condition, the lack of functional iduronate sulfatase enzyme results in an accumulation of dermatan sulfate and heparan sulfate in various tissues and organs, leading to progressive damage and a range of symptoms, including developmental delays, coarse facial features, hearing loss, heart problems, and joint stiffness.
Chondroitin sulfatases are a group of enzymes that break down chondroitin sulfate, which is a type of glycosaminoglycan (GAG) found in connective tissues such as cartilage, bone, and skin. Glycosaminoglycans are long, complex chains of sugars that help provide structure, hydration, and elasticity to these tissues.
Chondroitin sulfate is composed of alternating units of glucuronic acid and N-acetylgalactosamine, with various sulfate groups attached at different positions along the chain. Chondroitin sulfatases cleave specific bonds within this structure to help regulate the turnover and remodeling of GAGs in tissues.
There are several types of chondroitin sulfatases (designated as chondroitin sulfatase A, B, C, D, etc.), each with distinct substrate specificities and cellular localizations. Defects in these enzymes can lead to various genetic disorders, such as skeletal dysplasias and neurodegenerative diseases, due to the accumulation of unprocessed or partially degraded chondroitin sulfate in tissues.
Enzyme Replacement Therapy (ERT) is a medical treatment approach in which functional copies of a missing or deficient enzyme are introduced into the body to compensate for the lack of enzymatic activity caused by a genetic disorder. This therapy is primarily used to manage lysosomal storage diseases, such as Gaucher disease, Fabry disease, Pompe disease, and Mucopolysaccharidoses (MPS), among others.
In ERT, the required enzyme is produced recombinantly in a laboratory using biotechnological methods. The purified enzyme is then administered to the patient intravenously at regular intervals. Once inside the body, the exogenous enzyme is taken up by cells, particularly those affected by the disorder, and helps restore normal cellular functions by participating in essential metabolic pathways.
ERT aims to alleviate disease symptoms, slow down disease progression, improve quality of life, and increase survival rates for patients with lysosomal storage disorders. However, it does not cure the underlying genetic defect responsible for the enzyme deficiency.
I believe there might be a misunderstanding in your question. "Dogs" is not a medical term or condition. It is the common name for a domesticated carnivore of the family Canidae, specifically the genus Canis, which includes wolves, foxes, and other extant and extinct species of mammals. Dogs are often kept as pets and companions, and they have been bred in a wide variety of forms and sizes for different purposes, such as hunting, herding, guarding, assisting police and military forces, and providing companionship and emotional support.
If you meant to ask about a specific medical condition or term related to dogs, please provide more context so I can give you an accurate answer.
Factor VII, also known as proconvertin, is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor VII is synthesized in the liver and is activated when it comes into contact with tissue factor, which is exposed when blood vessels are damaged. Activated Factor VII then activates Factor X, leading to the formation of thrombin and ultimately a fibrin clot.
Inherited deficiencies or dysfunctions of Factor VII can lead to an increased risk of bleeding, while elevated levels of Factor VII have been associated with an increased risk of thrombosis (blood clots).
Sulfatases are a group of enzymes that play a crucial role in the metabolism of sulfated steroids, glycosaminoglycans (GAGs), and other sulfated molecules. These enzymes catalyze the hydrolysis of sulfate groups from these substrates, converting them into their respective unsulfated forms.
The human genome encodes for several different sulfatases, each with specificity towards particular types of sulfated substrates. For instance, some sulfatases are responsible for removing sulfate groups from steroid hormones and neurotransmitters, while others target GAGs like heparan sulfate, dermatan sulfate, and keratan sulfate.
Defects in sulfatase enzymes can lead to various genetic disorders, such as multiple sulfatase deficiency (MSD), X-linked ichthyosis, and mucopolysaccharidosis (MPS) type IIIC (Sanfilippo syndrome type C). These conditions are characterized by the accumulation of sulfated molecules in different tissues, resulting in progressive damage to multiple organs and systems.
Sly syndrome
Β-Glucuronidase
Flat-chested kitten syndrome
Vestronidase alfa
Hydrops fetalis
William S. Sly
Mucopolysaccharidosis
Ultragenyx
List of skin conditions
Chromosome 7
Macrocephaly
Pectus carinatum
List of geneticists
Alu element
Lysosomal storage disease
Hurler syndrome
NAGLU
N-sulfoglucosamine sulfohydrolase
Coarse facial features
Iduronidase
Genistein
Macroglossia
Maria Luisa Escolar
Sanfilippo syndrome
Galactosamine-6 sulfatase
Elizabeth F. Neufeld
Iduronate-2-sulfatase
List of diseases (M)
Arylsulfatase B
List of MeSH codes (C18)
Sly Syndrome (Mucopolysaccharidosis Type VII): Background, Pathophysiology, Epidemiology
Mucopolysaccharidoses Types I-VII Differential Diagnoses
Sly disease: Mucopolysaccharidosis type VII - Amrita Vishwa Vidyapeetham
Presentation of mucopolysaccharidosis VII (beta-glucuronidase deficiency) in infancy. | Journal of Medical Genetics
Mucopolysaccharidoses Types I-VII: Practice Essentials, Pathophysiology, Epidemiology
Mucopolysaccharidoses Types I-VII Medication: Enzymes
Mucopolysaccharidoses Types I-VII: Background, Pathophysiology, Epidemiology
Paw Print Genetics - Mucopolysaccharidosis VII (Shepherd Type) in the Dutch Shepherd
Treatment of a Lysosomal Storage Disease, Mucopolysaccharidosis VII, with Microencapsulated Recombinant Cells - McMaster...
Sly syndrome - Wikipedia
Improvement of skeletal lesions in mice with mucopolysaccharidosis type VII by neonatal adenoviral gene transfer<...
MedlinePlus: Genetic Conditions: G
Expanded Carrier Screening | Thermo Fisher Scientific - US
Lau YK[au] - Search Results - PubMed
Hydrops fetalis - CheckOrphan
Ultragenyx's (RARE) Q3 Earnings Miss Estimates, Revenues Up Y/Y
Wisdom Panel™ Premium dog DNA test | Most accurate breed detection
Embark Dog DNA Test - Breed
Biologics
NORWEGIAN FOREST CAT Archives - AnimaLabs©
Mucopolysaccharidosis type III: MedlinePlus Genetics
Embark Dog DNA Test - Breed
Pathways to Discovering the Cause of Disease: Could it be Genetic? - TUFTSBG2011 - VIN
MyDogDNA™
Search results - OMIA - Online Mendelian Inheritance in Animals
Feline PCR Genetic Tests - Veterinary Immunohistochemistry (IHC) Database
Deficiency7
- The mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders that are caused by a deficiency of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs), also known as mucopolysaccharides. (medscape.com)
- Presentation of mucopolysaccharidosis VII (beta-glucuronidase deficiency) in infancy. (bmj.com)
- A child is presented with mucopolysaccharidosis VII (beta-glucuronidase deficiency), bringing to six the number of reported patients with the infantile onset form of this disorder. (bmj.com)
- This child's course and data from published reports indicate that mucopolysaccharidosis VII, unlike the other known mucopolysaccharidoses, is clinically recognisable in the newborn period and is most likely to be associated with moderate mental deficiency which does not progress over time. (bmj.com)
- Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases, each of which is produced by an inherited deficiency of an enzyme involved in the degradation of acid mucopolysaccharides, now called glycosaminoglycans (GAGs). (medscape.com)
- Sly syndrome, also called mucopolysaccharidosis type VII (MPS-VII), is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase. (wikipedia.org)
- GALNS deficiency causes a block in the sequential breakdown of glycosaminoglycans N-acetylgalactosamine-6-sulfatase (GALNS) Morquio A (MPS IVA) Morquio B (MPS IVB) -D-Galactosidase Neufeld, EF and Muenzer, J. The Mucopolysaccharidoses. (slideserve.com)
Syndrome11
- Sly syndrome, also called mucopolysaccharidosis type VII (MPS VII), is a very rare lysosomal storage disease that has an autosomal-recessive inheritance pattern. (medscape.com)
- Sly syndrome is a rare form of mucopolysaccharidosis with an estimated worldwide frequency of 1 per 250,000 births. (medscape.com)
- A 7-year-old girl with Morquio syndrome and typical severe genu valgum. (medscape.com)
- However, Hurler syndrome is a severe form of the same heavy mucopolysaccharidosis, with affected children dying after several years, whereas Scheie disease has a mild clinical phenotype. (medscape.com)
- The onset of mucopolysaccharidosis type I-H (Hurler syndrome) occurs in early childhood (ie, 6-12 mo). (medscape.com)
- The defective gene responsible for Sly syndrome is located on chromosome 7. (wikipedia.org)
- Mepsevii is approved to treat Mucopolysaccharidosis VII (MPS VII), also known as Sly syndrome. (yahoo.com)
- Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a disorder that primarily affects the brain and spinal cord (central nervous system). (medlineplus.gov)
- Vestronidase alfa is used to treat some of the symptoms of a genetic condition called mucopolysaccharidosis VII (MYOO-koe-pol-ee-SAK-a-rye-DOE-sis Seven) or MPS VII, also called Sly syndrome. (astistrial.com)
- MEPSEVII is a recombinant human lysosomal beta glucuronidase indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome). (mepsevii.com)
- Although dentigerous cysts are highly prevalent, bilateral occurrence is rare and usually associated with syndromes or systemic diseases 1 , such as Maroteaux-Lamy syndrome 2 , cleidocranial dysplasia, and mucopolysaccharidosis 1 . (bvsalud.org)
Lysosomal storage1
- Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. (nih.gov)
Type11
- These diseases are autosomal recessive, except for mucopolysaccharidosis type II, which is X-linked. (medscape.com)
- Mucopolysaccharidosis (MPS) VII (shepherd type) is an inherited Lysosomal Storage Disorder affecting dogs. (pawprintgenetics.com)
- Clinical signs of MPS VII (shepherd type) are most commonly associated with accumulations in the bones and joints. (pawprintgenetics.com)
- Genetic testing of the GUSB gene will reliably determine whether a dog is a genetic Carrier of mucopolysaccharidosis VII (shepherd type). (pawprintgenetics.com)
- Mucopolysaccharidosis VII (shepherd type) is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. (pawprintgenetics.com)
- Molecular diagnostic tests for ascertainment of genotype at the mucopolysaccharidosis type VII locus in dogs. (pawprintgenetics.com)
- The severity of obstructive sleep apnea varies with each type of mucopolysaccharidosis. (medscape.com)
- Results of a study of Bradley et al revealed worsening linear growth over time in individuals with mucopolysaccharidosis type II and type VI and significantly elevated body mass index standard deviation score. (medscape.com)
- We have used the beta-glucuronidase-deficient mouse model of mucopolysaccharidosis type VII (MPS VII) to develop an alternative approach to therapy. (mcmaster.ca)
- Mucopolysaccharidosis type IVA (Morquio A disease):clinical review and current treatment. (slideserve.com)
- Treatment of mucopolysaccharidosis type I is enzyme replacement with laronidase , which effectively halts progression and reverses all non-central nervous system complications of the disease. (msdmanuals.com)
Chromosome1
- The beta-glucuronidase ( GUSB) gene (OMIM *611499) is located on the long arm of chromosome 7 (7q), at band q11.21. (medscape.com)
Beta-glucuronidase4
- Beta-glucuronidase-deficient mucopolysaccharidosis in the dog. (pawprintgenetics.com)
- Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells. (pawprintgenetics.com)
- Using this strategy, we injected beta-glucuronidase-secreting fibroblasts enclosed in alginate microcapsules into mutant MPS VII mice. (mcmaster.ca)
- However, implanted mutant MPS VII mice developed antibodies against the murine beta-glucuronidase, demonstrating a potential obstacle in patients with a null mutation who react against the replaced enzyme as a foreign antigen. (mcmaster.ca)
Genetic2
- Body size is a strong genetic influence: for example, a seven year old Great Dane is at the start of his golden years, but a seven year old Pomeranian is just learning what "slow down" means. (embarkvet.com)
- We analyze your dog's DNA and provide you with a genetic profile within 7-10 business days of receiving your dog's sample. (veripet.org)
Enzyme2
- MPS VII is a metabolic disorder in which the body lacks the enzyme needed to break down certain natural substances. (astistrial.com)
- Lysosomal disorders like mucopolysaccharidosis are triggered when a particular enzyme exists in too small amount or it is missing altogether. (mpstarsasag.hu)
Glycosaminoglycans3
- [ 7 ] The accumulation of glycosaminoglycans in the vocal source leading to unbalanced enlargement can exhibit pathological jitter and shimmer. (medscape.com)
- Mucopolysaccharidosis (MPS) involves defective activity of the lysosomal enzymes that degrade mucopolysaccharides (glycosaminoglycans [GAGs] attached to a link protein with a hyaluronic acid core) into smaller components. (medscape.com)
- Diagnosis of mucopolysaccharidoses is suggested by history, physical examination, bone abnormalities (eg, dysostosis multiplex) found during skeletal survey, and elevated total and fractionated urinary glycosaminoglycans. (msdmanuals.com)
Coagulation1
- 7. Coagulation factor IX recombinant Fc fusion protein ( Alprolix , Bioverativ), the first long-acting hemophilia B drug approved by the FDA for use in children and adults with hemophilia B. It has a list price of about $503,800 per year. (medscape.com)
Gangliosidoses1
- Thus the brain, which is rich in gangliosides, is particularly affected by gangliosidoses, whereas mucopolysaccharidoses affect many tissues because mucopolysaccharides are present throughout the body. (msdmanuals.com)
Diagnosis1
- Extremely low levels of β-glucuronidase confirmed the diagnosis of Sly disease (Mucopolysaccharidosis VII). (amrita.edu)
Infancy1
- Mucopolysaccharidosis usually manifests during infancy or early childhood. (medscape.com)
Mepsevii1
- The effect of MEPSEVII on the central nervous system manifestations of MPS VII has not been determined. (mepsevii.com)
Symptoms1
- The life expectancy of individuals with MPS VII varies depending on the symptoms. (wikipedia.org)
Individuals1
- The elevated body mass index in individuals with mucopolysaccharidosis is a risk factor for long-term cardiovascular disease. (medscape.com)
Types3
- All types of mucopolysaccharidoses are linked with thickened and inelastic-appearing skin. (medscape.com)
- Hematopoietic stem cell transplant (HSCT) has been used to treat other types of MPS diseases, but this is not yet available for MPS-VII. (wikipedia.org)
- The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. (medlineplus.gov)
Form1
- The phenotypic spectrum of mucopolysaccharidosis IVA (MPS IVA) is a continuum that ranges from a severe and rapidly progressive early-onset form to a slowly progressive later-onset form. (nih.gov)
Proteins1
- Methods toward simplification of time resolved fluorescence anisotropy in proteins labeled with NBD (4-chloro-7-nitrobenzofurazan) adducts. (ucla.edu)
Treatment1
- Animal experiments suggest that HSCT may be an effective treatment for MPS-VII in humans. (wikipedia.org)
Common1
- Obstructive respiratory problems are common in patients with mucopolysaccharidosis. (medscape.com)
Patients5
- Tonsillar hypertrophy is a typical symptom in patients with mucopolysaccharidoses. (medscape.com)
- La base de données consacrée à l'administration des patients et à l'activité biostatistique a été interrogée pour l'ensemble des patients de moins de 15 ans qui avaient consulté à l'hôpital de campagne militaire marocain dans la Bande de Gaza entre novembre 2012 et février 2013 et les données obtenues ont été passées en revue. (who.int)
- Les patients pédiatriques souffrant de traumatismes potentiellement fatals constituent une partie de la responsabilité première des établissements de santé militaires en temps de guerre. (who.int)
- All relevant information A total of 37 227 patients consulted the field hospital is a medical-surgical hos- on the patients gathered in the consulta- field hospital, of whom 7 420 (19.9%) pital, equipped with specialized medi- tion and in conversation with the par- were children aged 15 years. (who.int)
- 9. Galsulfase ( Naglazyme , Biomarin Phamaceutical), approved in 2005 to improve walking and stair-climbing capacity of patients with mucopolysaccharidosis VI . (medscape.com)
Adult1
- So going back to our Dane/Pom example, we'd estimate a seven year old Great Dane at about 80 years old (senior citizen), but a seven year old Pom would be about 42 (adult). (embarkvet.com)
Children1
- Obstructive sleep apnea reportedly is a finding in children with mucopolysaccharidoses. (medscape.com)
Important1
- The most important are the mucopolysaccharidoses and sphingolipidoses. (msdmanuals.com)
Year1
- Just within this example, you can see that the old "one doggie year = seven human years" adage isn't going to work. (embarkvet.com)