Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI
Mucopolysaccharidosis III
Glycosaminoglycans
Mucopolysaccharidosis II
Enzyme Replacement Therapy
Electrophoresis, Cellulose Acetate
Iduronate Sulfatase
Iduronidase
Corneal Opacity
Mucolipidoses
Methylene Blue
Joint Diseases
Fluorometric measurement of urinary alpha-L-iduronidase activity. (1/155)
A fluorogenic substrate for alpha-L-iduronidase, 4-methylumbelliferyl alpha-L-iduronide, has been newly synthesized and the enzyme activity has been measured in urine samples obtained from normal persons and patients suffering from mucopolysaccharidosis. Urine samples derived from a patient with Scheie syndrome showed greatly reduced activity compared with a normal adult at a similar age. This patient exhibited a high level of urinary excretion of dermatan sulfate and heparan sulfate, which could be interpreted in terms of her low alpha-L-iduronidase activity. The use of the fluorogenic substrate has some advantages over existing methods because of the high sensitivity and the relative ease of handling, and it should be useful not only for diagnosis but also for following the purification process of the enzyme. (+info)Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. (2/155)
Hyaluronan (HA), a large glycosaminoglycan abundant in the extracellular matrix, is important in cell migration during embryonic development, cellular proliferation, and differentiation and has a structural role in connective tissues. The turnover of HA requires endoglycosidic breakdown by lysosomal hyaluronidase, and a congenital deficiency of hyaluronidase has been thought to be incompatible with life. However, a patient with a deficiency of serum hyaluronidase, now designated as mucopolysaccharidosis IX, was recently described. This patient had a surprisingly mild clinical phenotype, including notable periarticular soft tissue masses, mild short stature, an absence of neurological or visceral involvement, and histological and ultrastructural evidence of a lysosomal storage disease. To determine the molecular basis of mucopolysaccharidosis IX, we analyzed two candidate genes tandemly distributed on human chromosome 3p21.3 and encoding proteins with homology to a sperm protein with hyaluronidase activity. These genes, HYAL1 and HYAL2, encode two distinct lysosomal hyaluronidases with different substrate specificities. We identified two mutations in the HYAL1 alleles of the patient, a 1412G --> A mutation that introduces a nonconservative amino acid substitution (Glu268Lys) in a putative active site residue and a complex intragenic rearrangement, 1361del37ins14, that results in a premature termination codon. We further show that these two hyaluronidase genes, as well as a third recently discovered adjacent hyaluronidase gene, HYAL3, have markedly different tissue expression patterns, consistent with differing roles in HA metabolism. These data provide an explanation for the unexpectedly mild phenotype in mucopolysaccharidosis IX and predict the existence of other hyaluronidase deficiency disorders. (+info)Analysis of glycosaminoglycans in urine by using acridine orange fluorescence. (3/155)
The fluorescence technique described here utilizes the electrostatic interaction between the polyanionic sites of glycosaminoglycans and the cationic dye Acridine Orange to analyse urinary glycosaminoglycans from patients suffering from mucopolysaccharidoses. The basis of the titration is the decrease in the fluorescence of free Acridine Orange that occurs when it is bound to polyanions. The effect of the presence of possible interfering materials such as salt, proteins and trace materials in urine was evaluated. This fluorescence technique is technically simple. (+info)Report of a mucopolysaccharidosis occurring in Australian aborigines. (4/155)
The first 2 reported cases of a mucopolysaccharidosis occurring in an Australian aboriginal family are presented. Though these children had the characteristic morphological features of the Hurler syndrome, enzyme assay of cultured fibroblasts showed normal levels of alpha-L-iduronidase and decreased activity of arylsulphatase B. Thus, they represented the Hurler syndrome clinically, while they had the enzyme defect of the Maroteaux-Lamy syndrome, and they may represent a new severe form of the Maroteaux-Lamy syndrome. The parents of these children were first cousins. Though the children were not full blood aborigines, examination of the pedigree indicates that the gene originated in the common aboriginal family. (+info)Chondroitin 4- and 6-sulfaturia: a new type of inborn error of metabolism? (5/155)
A 14-year-old boy was found to excrete excessive amounts of acidic glycosaminoglycans which were predominantly chondroitin 4-sulfate and chondroitin 6-sulfate. Clinical features included dwarfism, mental retardation, coarse facies, deformities of the spine, hip joints and thorax, and granulations in leucocytes. The clinical and biochemical features found in this boy were compared with the known types of mucopolysaccharidosis and it has been concluded that this case is a new type of mucopolysacchariduria. (+info)Metabolic cardiomyopathies. (6/155)
The energy needed by cardiac muscle to maintain proper function is supplied by adenosine Ariphosphate primarily (ATP) production through breakdown of fatty acids. Metabolic cardiomyopathies can be caused by disturbances in metabolism, for example diabetes mellitus, hypertrophy and heart failure or alcoholic cardiomyopathy. Deficiency in enzymes of the mitochondrial beta-oxidation show a varying degree of cardiac manifestation. Aberrations of mitochondrial DNA lead to a wide variety of cardiac disorders, without any obvious correlation between genotype and phenotype. A completely different pathogenetic model comprises cardiac manifestation of systemic metabolic diseases caused by deficiencies of various enzymes in a variety of metabolic pathways. Examples of these disorders are glycogen storage diseases (e.g. glycogenosis type II and III), lysosomal storage diseases (e.g. Niemann-Pick disease, Gaucher disease, I-cell disease, various types of mucopolysaccharidoses, GM1 gangliosidosis, galactosialidosis, carbohydrate-deficient glycoprotein syndromes and Sandhoff's disease). There are some systemic diseases which can also affect the heart, for example triosephosphate isomerase deficiency, hereditary haemochromatosis, CD 36 defect or propionic acidaemia. (+info)Clinical and laboratorial study of 19 cases of mucopolysaccharidoses. (7/155)
The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of lysosomal glycosaminoglycan (GAG) metabolism. The importance of this group of disorders among the inborn errors of metabolism led us to report 19 cases. METHOD: We performed clinical, radiological, and biochemical evaluations of the suspected patients, which allowed us to establish a definite diagnosis in 19 cases. RESULTS: Not all patients showed increased GAG levels in urine; enzyme assays should be performed in all cases with strong clinical suspicion. The diagnosis was made on average at the age of 48 months, and the 19 MPS cases, after a full clinical, radiological, and biochemical study, were classified as follows: Hurler - MPS I (1 case); Hunter - MPS II (2 cases); Sanfilippo - MPS III (2 cases); Morquio - MPS IV (4 cases); Maroteaux-Lamy - MPS VI (9 cases); and Sly - MPS VII (1 case). DISCUSSION: The high relative frequency of Maroteaux-Lamy disease contrasts with most reports in the literature and could express a population variability. (+info)Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency. (8/155)
Patients with mannosidosis, an inherited deficiency of lysosomal alpha-mannosidase, accumulate large amounts of mannose-rich oligosaccharides (the "core" of the carbohydrate units of many glocoproteins) in brain and liver and excrete these partial degradation products in their urine. A profound alpha-mannosidase deficiency was demonstrated in fibroblasts cultured from a skin biopsy obtained from a child with mannosidosis. Further, abnormal glycopeptides rich in mannose and similar to oligosaccharides found in the patient's urine were isolated from fibroblast extracts by a variety of chromatographic procedures and by virtue of their binding to a concanavalin A-Sepharose 4B affinity column. This storage material contained mannose, N-acetylglucosamine, and asparagine in the ratio 3 : 1 : 1 together with a few toher amino acids and had a molecular weight of approximately 1,100. There was no evidence for excretion of storage material by mannosidosis fibroblasts or for any abnormality in cell surface glycoprotein composition. The glycopeptide nature of the storage material isolated from cultured skin fibroblasts may be attributed to the low level of N-aspartyl-beta-glucosamindase (EC 3.5.1.-) activity in these cells. (+info)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.
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 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.
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.
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.
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.
Dysostosis is a term used to describe a group of genetic disorders that are characterized by abnormal development and formation of one or more bones in the body. The condition is typically present at birth (congenital) and can affect any bone, but it most commonly involves the bones of the skull, face, hands, and feet.
The term "dysostosis" comes from the Greek words "dys," meaning difficult or abnormal, and "osteon," meaning bone. Dysostoses are usually caused by mutations in specific genes that regulate bone development. These genetic changes can be inherited from one or both parents or can occur spontaneously during fetal development.
There are many different types of dysostoses, each with its own set of symptoms and characteristics. Some common examples include:
1. Cleidocranial Dysplasia: This is a rare genetic disorder that affects the development of the skull and collarbones (cleido). People with cleidocranial dysplasia may have a larger than normal head, wide-set eyes, a prominent forehead, and underdeveloped or missing collarbones.
2. Acrocephalopolysyndactyly Type II: Also known as ACPS II or Greig cephalopolysyndactyly syndrome, this disorder is characterized by a pointed skull (acrocephaly), extra fingers and toes (polydactyly), and wide-set eyes.
3. Osteogenesis Imperfecta: This is a group of genetic disorders that affect the body's production of collagen, a protein that helps to strengthen bones. People with osteogenesis imperfecta have fragile bones that break easily, often as a result of minor trauma.
4. Diastrophic Dysplasia: This is a rare genetic disorder that affects the development of the bones and cartilage in the body. People with diastrophic dysplasia may have short limbs, a deformed spine, and a characteristic "hitchhiker's thumb" appearance.
5. Thanatophoric Dysplasia: This is a severe genetic disorder that affects the development of the bones in the body. People with thanatophoric dysplasia have very short limbs, a small chest, and a deformed skull. The condition is often fatal in infancy or early childhood.
These are just a few examples of the many different types of skeletal dysplasias that exist. While some forms of these disorders can be managed with medical treatment and therapy, others may require surgery or other interventions to help improve quality of life. In some cases, genetic counseling and testing may be recommended for individuals who are considering starting a family and have a history of skeletal dysplasia in their family.
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.
Electrophoresis, cellulose acetate is a laboratory technique used to separate and analyze proteins or other charged molecules based on their size and charge. The sample is applied to a sheet of cellulose acetate, a type of porous plastic film, and an electric field is applied. The proteins migrate through the film towards the electrode with the opposite charge, with smaller and more negatively charged molecules moving faster than larger and less negatively charged ones. This allows for the separation and identification of different protein components in a mixture. It is a simple and rapid method for routine protein separations and is commonly used in biochemistry and molecular biology research.
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.
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.
Corneal opacity refers to a condition in which the cornea, the clear front part of the eye, becomes cloudy or opaque. This can occur due to various reasons such as injury, infection, degenerative changes, or inherited disorders. As a result, light is not properly refracted and vision becomes blurred or distorted. In some cases, corneal opacity can lead to complete loss of vision in the affected eye. Treatment options depend on the underlying cause and may include medication, corneal transplantation, or other surgical procedures.
Mucolipidoses are a group of inherited metabolic disorders characterized by the accumulation of complex carbohydrates (muco-) and fatty substances (lipids) in various tissues and cells (-oses). This is due to deficiency in enzymes that help break down these substances within lysosomes, which are organelles responsible for recycling and breaking down waste materials inside the cell.
There are four main types of mucolipidoses (I, II, III, and IV), each resulting from specific genetic mutations affecting different enzymes or proteins involved in the lysosomal degradation pathway. The symptoms, severity, and age of onset can vary widely among these types, ranging from mild to severe and including developmental delays, bone abnormalities, vision and hearing loss, heart problems, and coarse facial features.
Mucolipidoses are typically inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. However, mucolipidosis II is caused by X-linked inheritance, where a single copy of the mutated gene on the X chromosome is enough to cause the disorder.
Early diagnosis and management of mucolipidoses can help improve quality of life and slow disease progression. Treatment options include physical therapy, occupational therapy, speech therapy, medications for symptom management, and in some cases, enzyme replacement therapy or bone marrow transplantation.
Methylene Blue is a heterocyclic aromatic organic compound with the molecular formula C16H18ClN3S. It is primarily used as a medication, but can also be used as a dye or as a chemical reagent. As a medication, it is used in the treatment of methemoglobinemia (a condition where an abnormal amount of methemoglobin is present in the blood), as well as in some forms of poisoning and infections. It works by acting as a reducing agent, converting methemoglobin back to hemoglobin, which is the form of the protein that is responsible for carrying oxygen in the blood. Methylene Blue has also been used off-label for other conditions, such as vasculitis and Alzheimer's disease, although its effectiveness for these uses is not well established.
It is important to note that Methylene Blue should be used with caution, as it can cause serious side effects in some people, particularly those with kidney or liver problems, or those who are taking certain medications. It is also important to follow the instructions of a healthcare provider when using this medication, as improper use can lead to toxicity.
Joint diseases is a broad term that refers to various conditions affecting the joints, including but not limited to:
1. Osteoarthritis (OA): A degenerative joint disease characterized by the breakdown of cartilage and underlying bone, leading to pain, stiffness, and potential loss of function.
2. Rheumatoid Arthritis (RA): An autoimmune disorder causing inflammation in the synovial membrane lining the joints, resulting in swelling, pain, and joint damage if left untreated.
3. Infectious Arthritis: Joint inflammation caused by bacterial, viral, or fungal infections that spread through the bloodstream or directly enter the joint space.
4. Gout: A type of arthritis resulting from the buildup of uric acid crystals in the joints, typically affecting the big toe and characterized by sudden attacks of severe pain, redness, and swelling.
5. Psoriatic Arthritis (PsA): An inflammatory joint disease associated with psoriasis, causing symptoms such as pain, stiffness, and swelling in the joints and surrounding tissues.
6. Juvenile Idiopathic Arthritis (JIA): A group of chronic arthritis conditions affecting children, characterized by joint inflammation, pain, and stiffness.
7. Ankylosing Spondylitis: A form of arthritis primarily affecting the spine, causing inflammation, pain, and potential fusion of spinal vertebrae.
8. Bursitis: Inflammation of the fluid-filled sacs (bursae) that cushion joints, leading to pain and swelling.
9. Tendinitis: Inflammation or degeneration of tendons, which connect muscles to bones, often resulting in pain and stiffness near joints.
These conditions can impact the function and mobility of affected joints, causing discomfort and limiting daily activities. Proper diagnosis and treatment are essential for managing joint diseases and preserving joint health.